{ "schema_version": "0.8.0", "title": "Long COVID treatments & trials", "as_of": "2026-10-14", "timezone": "America/Toronto", "editorial_status": "research_draft", "clinical_review": { "status": "not_performed", "reviewer": null, "date": null, "required_for_research_preview": false, "decision": "Independent clinical review deferred for now; retain sourced research summaries, limitations and a prominent medical-information notice.", "decision_date": "2026-10-13" }, "scope": "Curated twenty-one-treatment beta; not an exhaustive evidence review or prescribing guide.", "sources": [ { "id": "prevail-registry", "title": "PREVAIL-LC registry and posted results", "url": "https://clinicaltrials.gov/study/NCT06161688?tab=results", "type": "registry_results", "source_updated": "2026-04-02", "retrieved": "2026-10-13" }, { "id": "prevail-ucsf", "title": "UCSF PREVAIL-LC study page", "url": "https://clinicaltrials.ucsf.edu/trial/NCT06161688", "type": "investigator_page", "retrieved": "2026-10-13" }, { "id": "recover-appendix", "title": "RECOVER-AUTONOMIC ivabradine appendix", "url": "https://clinicaltrials.gov/study/NCT06305806", "type": "registry", "source_updated": "2026-02-20", "retrieved": "2026-10-13" }, { "id": "recover-platform", "title": "RECOVER-AUTONOMIC platform results — enrolment", "url": "https://clinicaltrials.gov/study/NCT06305780?tab=results", "type": "registry_enrolment_results", "source_updated": "2026-08-03", "retrieved": "2026-10-13" }, { "id": "recover-announcement", "title": "RECOVER investigator results announcement", "url": "https://recovercovid.org/news/recover-autonomic-clinical-trial-results-shared-2026-acc-conference", "type": "investigator_announcement", "published": "2026-03-28", "retrieved": "2026-10-13" }, { "id": "recover-seminar", "title": "RECOVER July 2026 investigator seminar transcript", "url": "https://recovercovid.org/r3-seminar-series/recover-clinical-trial-results-and-pursuit-long-covid-treatments/audio-transcript", "type": "investigator_presentation", "published": "2026-07-14", "retrieved": "2026-10-13" }, { "id": "iva-observational", "title": "Abdelnabi et al. 2023 prospective observational study", "url": "https://pubmed.ncbi.nlm.nih.gov/37469536/", "type": "peer_reviewed_abstract", "published": "2023-06-25", "retrieved": "2026-10-13" }, { "id": "coviva-registry", "title": "COVIVA registry", "url": "https://clinicaltrials.gov/study/NCT05481177", "type": "registry", "source_updated": "2023-11-29", "retrieved": "2026-10-13" }, { "id": "coviva-protocol", "title": "COVIVA study protocol — not a results report", "url": "https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1550636/full", "type": "peer_reviewed_protocol", "published": "2025-07-07", "retrieved": "2026-10-13" }, { "id": "oaktree-paper", "title": "OAKTREE acute-COVID randomized trial results", "url": "https://pubmed.ncbi.nlm.nih.gov/40675167/", "type": "peer_reviewed_abstract", "retrieved": "2026-10-13" }, { "id": "birch-paper", "title": "BIRCH acute-COVID randomized trial results", "url": "https://pubmed.ncbi.nlm.nih.gov/40694627/", "type": "peer_reviewed_abstract", "retrieved": "2026-10-13" }, { "id": "oaktree-registry", "title": "OAKTREE registry and results", "url": "https://clinicaltrials.gov/study/NCT05715528?tab=results", "type": "registry_results", "source_updated": "2024-12-24", "retrieved": "2026-10-13" }, { "id": "birch-registry", "title": "BIRCH registry and results", "url": "https://clinicaltrials.gov/study/NCT05603143?tab=results", "type": "registry_results", "source_updated": "2024-12-20", "retrieved": "2026-10-13" }, { "id": "lancora-dpd", "title": "Health Canada Lancora marketed product record", "url": "https://health-products.canada.ca/dpd-bdpp/info?code=94728&lang=eng", "type": "regulatory_record", "retrieved": "2026-10-13" }, { "id": "lancora-monograph", "title": "Health Canada Lancora product monograph", "url": "https://pdf.hres.ca/dpd_pm/00080705.PDF", "type": "product_monograph", "source_updated": "2025-05-30", "retrieved": "2026-10-13" }, { "id": "sap", "title": "Health Canada Special Access Program", "url": "https://www.canada.ca/en/health-canada/services/drugs-health-products/special-access/drugs.html", "type": "official_access_guidance", "retrieved": "2026-10-13" }, { "id": "prevail-protocol-sap", "title": "PREVAIL-LC protocol and statistical analysis plan", "url": "https://cdn.clinicaltrials.gov/large-docs/88/NCT06161688/Prot_SAP_000.pdf", "type": "protocol_and_statistical_analysis_plan", "retrieved": "2026-10-13", "protocol_version": "1.6", "protocol_date": "2024-12-05", "sap_finalized": "2025-02-21" }, { "id": "recover-acc-slides", "title": "Taub: RECOVER-AUTONOMIC ACC.26 presentation (slides 14 and 16)", "url": "https://clinicaltrialresults.org/wp-content/uploads/2026/03/Taub.pdf", "type": "investigator_conference_slides", "retrieved": "2026-10-13", "published": "2026-03-28" }, { "id": "ontario-iva-lu", "title": "Ontario ivabradine 5 mg limited-use criteria, code 538", "url": "https://www.formulary.health.gov.on.ca/formulary/limitedUseNotes.xhtml?pcg9Id=240400174", "type": "provincial_formulary", "retrieved": "2026-10-13" }, { "id": "obeldesivir-all-trials", "title": "ClinicalTrials.gov: obeldesivir, all conditions", "url": "https://clinicaltrials.gov/api/v2/studies?query.intr=obeldesivir&pageSize=100&countTotal=true", "type": "registry_search", "retrieved": "2026-10-13" }, { "id": "gilead-june-2026", "title": "Gilead June 2026 statement identifying obeldesivir as investigational", "url": "https://investors.gilead.com/news/news-details/2026/Gilead-Mobilizes-Rapid-Donation-of-Remdesivir-to-Support-Ebola-Response-Building-on-Decade-Long-Commitment-to-Outbreak-Relief/default.aspx", "type": "manufacturer_statement", "retrieved": "2026-10-13", "published": "2026-06-12" }, { "id": "coviva-institution", "title": "Uniformed Services University: MiCOR research projects", "url": "https://medschool.usuhs.edu/med/research/micor-data-science", "type": "institutional_project_listing", "retrieved": "2026-10-13" }, { "id": "stop-pasc-paper", "title": "STOP-PASC randomized trial (2024)", "url": "https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2819901", "type": "peer_reviewed_results", "retrieved": "2026-10-13" }, { "id": "paxlc-paper", "title": "PAX LC randomized trial (2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/40188838/", "type": "peer_reviewed_results", "retrieved": "2026-10-13" }, { "id": "vital-paper", "title": "RECOVER-VITAL randomized trial (August 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/42673984/", "type": "peer_reviewed_results", "retrieved": "2026-10-13" }, { "id": "pax-canada", "title": "Health Canada: Paxlovid acute-COVID authorization", "url": "https://www.canada.ca/en/health-canada/news/2022/01/health-canada-authorizes-paxlovidtm-for-patients-with-mild-to-moderate-covid-19-at-high-risk-of-developing-serious-disease.html", "type": "official_authorization", "retrieved": "2026-10-13" }, { "id": "pax-interactions", "title": "Health Canada: Paxlovid interactions", "url": "https://www.canada.ca/en/health-canada/services/drugs-health-products/medeffect-canada/health-product-infowatch/march-2023.html", "type": "official_safety_information", "retrieved": "2026-10-13" }, { "id": "ldn-paper", "title": "Bonilla et al.: retrospective LDN cohort (2023)", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11028858/", "type": "peer_reviewed_observational_results", "retrieved": "2026-10-13" }, { "id": "ivig-paper", "title": "McAlpine et al.: post-COVID small-fibre neuropathy (2024)", "url": "https://recovercovid.org/publications/case-control-study-individuals-small-fiber-neuropathy-after-covid-19", "type": "peer_reviewed_observational_abstract", "retrieved": "2026-10-13" }, { "id": "revitalize-canada", "title": "Health Canada: LC-REVITALIZE authorization", "url": "https://clinical-trials-search.canada.ca/en/clinical-trial/295288-long-covid", "type": "official_trial_authorization", "retrieved": "2026-10-13" }, { "id": "nct05576662", "title": "STOP-PASC registry", "url": "https://clinicaltrials.gov/study/NCT05576662", "type": "trial_registry", "retrieved": "2026-10-13" }, { "id": "nct05668091", "title": "PAX LC registry", "url": "https://clinicaltrials.gov/study/NCT05668091", "type": "trial_registry", "retrieved": "2026-10-13" }, { "id": "nct05965726", "title": "RECOVER-VITAL registry", "url": "https://clinicaltrials.gov/study/NCT05965726", "type": "trial_registry", "retrieved": "2026-10-13" }, { "id": "nct05430152", "title": "BC low-dose naltrexone trial registry", "url": "https://clinicaltrials.gov/study/NCT05430152", "type": "trial_registry", "retrieved": "2026-10-13" }, { "id": "nct06366724", "title": "LIFT registry", "url": "https://clinicaltrials.gov/study/NCT06366724", "type": "trial_registry", "retrieved": "2026-10-13" }, { "id": "nct06305793", "title": "RECOVER-AUTONOMIC IVIG registry", "url": "https://clinicaltrials.gov/study/NCT06305793", "type": "trial_registry", "retrieved": "2026-10-13" }, { "id": "nct05350774", "title": "NIH neurological Long COVID IVIG study registry", "url": "https://clinicaltrials.gov/study/NCT05350774", "type": "trial_registry", "retrieved": "2026-10-13" }, { "id": "nct06928272", "title": "LC-REVITALIZE registry", "url": "https://clinicaltrials.gov/study/NCT06928272", "type": "trial_registry", "retrieved": "2026-10-14", "source_updated": "2026-10-06" }, { "id": "vital-full", "title": "RECOVER-VITAL full report: Results and Table 3", "url": "https://www.sciencedirect.com/science/article/pii/S1473309926004068", "type": "peer_reviewed_full_results", "retrieved": "2026-10-13" }, { "id": "lift-protocol", "title": "LIFT peer-reviewed protocol (12 August 2026)", "url": "https://link.springer.com/article/10.1186/s13063-026-09943-6", "type": "peer_reviewed_protocol", "retrieved": "2026-10-13" }, { "id": "revitalize-quebec", "title": "Recherche Santé Québec: LC-REVITALIZE site listings", "url": "https://recherchesantequebec.ca/public/projects/451590", "type": "registry_derived_regional_listing", "retrieved": "2026-10-13", "provenance": "Page identifies ClinicalTrials.gov as origin; not independent investigator confirmation." }, { "id": "stimulate-drug-paper", "title": "STIMULATE-ICP drug trial — full published report (2026)", "url": "https://discovery.ucl.ac.uk/id/eprint/10228344/1/Wall%20et%20al%202026.pdf", "type": "peer_reviewed_randomized_trial", "published": "2026-07-08", "retrieved": "2026-10-14" }, { "id": "colchicine-india-paper", "title": "Colchicine randomized trial — India (2025)", "url": "https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2840468", "type": "peer_reviewed_randomized_trial", "published": "2025-10-20", "retrieved": "2026-10-14" }, { "id": "hbot-israel-paper", "title": "HBOT 40-session randomized trial (2022)", "url": "https://www.nature.com/articles/s41598-022-15565-0", "type": "peer_reviewed_randomized_trial", "retrieved": "2026-10-14" }, { "id": "hbot-hotloco-paper", "title": "HOT-LoCO 10-session randomized trial (2025)", "url": "https://bmjopen.bmj.com/content/15/4/e094386", "type": "peer_reviewed_randomized_trial", "retrieved": "2026-10-14" }, { "id": "hbot-belgium-paper", "title": "Belgian four-group oxygen trial (2025)", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12267068/", "type": "peer_reviewed_randomized_trial", "retrieved": "2026-10-14" }, { "id": "reclaim-interventions", "title": "RECLAIM investigator intervention page", "url": "https://www.reclaimtrial.ca/current-interventions", "type": "investigator_page", "retrieved": "2026-10-14" }, { "id": "reclaim-hbot-registry", "title": "RECLAIM HBOT registry", "url": "https://clinicaltrials.gov/study/NCT06452095", "type": "registry", "source_updated": "2026-02-23", "retrieved": "2026-10-13" }, { "id": "sunnybrook-hbot-registry", "title": "Sunnybrook HBOT registry", "url": "https://clinicaltrials.gov/study/NCT06082518", "type": "registry", "source_updated": "2026-09-02", "retrieved": "2026-10-13" }, { "id": "taurine-biomarker", "title": "Taurine biomarker study — observational (2024)", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11152273/", "type": "observational_biomarker_study", "retrieved": "2026-10-14" }, { "id": "pirfenidone-fibro", "title": "FIBRO-COVID randomized trial — post-pneumonia lung fibrosis", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12018760/", "type": "peer_reviewed_randomized_trial", "retrieved": "2026-10-14" }, { "id": "pirfenidone-correction", "title": "FIBRO-COVID correction — author affiliation only (2026)", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13419979/", "type": "correction", "retrieved": "2026-10-14" }, { "id": "hiox-pilot-abstract", "title": "Hi-OxSR open-label pilot abstract — manufacturer-hosted copy", "url": "https://12thmantec.com/wp-content/uploads/2025/07/2.-2024-Parhizgar-Hi-Ox-Pilot-Trial-abstract.pdf", "type": "pilot_abstract", "retrieved": "2026-10-14" }, { "id": "sgb-parosmia", "title": "Stellate ganglion block randomized parosmia trial (2025)", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12163713/", "type": "peer_reviewed_randomized_trial", "retrieved": "2026-10-14" }, { "id": "sgb-cohort", "title": "Stellate ganglion block retrospective cohort (2025)", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12374758/", "type": "retrospective_cohort", "retrieved": "2026-10-14" }, { "id": "nct06721949", "title": "Taurine Supplementation in Long COVID — registry", "url": "https://clinicaltrials.gov/study/NCT06721949", "type": "registry", "source_updated": "2026-09-18", "retrieved": "2026-10-14" }, { "id": "nct06928506", "title": "Effect of Hi-OxSR for the Treatment of Post COVID Condition — registry", "url": "https://clinicaltrials.gov/study/NCT06928506", "type": "registry", "source_updated": "2025-09-15", "retrieved": "2026-10-14" }, { "id": "nct07374562", "title": "Stellate Ganglion Block for Long COVID Symptoms: A Randomized Controlled Trial — registry", "url": "https://clinicaltrials.gov/study/NCT07374562", "type": "registry", "source_updated": "2026-02-09", "retrieved": "2026-10-14" }, { "id": "nct07468604", "title": "Cervicothoracic Sympathetic Block Evaluation for Post COVID Condition — registry", "url": "https://clinicaltrials.gov/study/NCT07468604", "type": "registry", "source_updated": "2026-10-09", "retrieved": "2026-10-14" }, { "id": "nct07682402", "title": "Taurine Supplementation in Adolescents With Post-COVID Condition — registry", "url": "https://clinicaltrials.gov/study/NCT07682402", "type": "registry", "source_updated": "2026-08-13", "retrieved": "2026-10-14" }, { "id": "guanfacine-nac-series", "title": "Guanfacine + NAC: 12-patient case series (online 2022)", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC9691274/", "type": "published_case_series", "published": "2022-11-25", "retrieved": "2026-10-14" }, { "id": "guanfacine-case", "title": "Guanfacine alone: single-patient report (2024)", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11544435/", "type": "published_case_report", "published": "2024-06-27", "retrieved": "2026-10-14" }, { "id": "guanfacine-survey", "title": "Patient-reported treatment survey (2025)", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12280984/", "type": "published_patient_survey", "published": "2025-07-08", "retrieved": "2026-10-14" }, { "id": "guanfacine-registry-search", "title": "ClinicalTrials.gov: guanfacine and Long COVID search", "url": "https://clinicaltrials.gov/api/v2/studies?query.intr=guanfacine&query.cond=Long%20COVID&pageSize=100&countTotal=true", "type": "registry_search", "retrieved": "2026-10-14" }, { "id": "guanfacine-all-search", "title": "ClinicalTrials.gov: guanfacine across conditions", "url": "https://clinicaltrials.gov/api/v2/studies?query.intr=guanfacine&fields=NCTId,BriefTitle,Condition,InterventionName,OverallStatus&pageSize=100&countTotal=true", "type": "registry_search", "retrieved": "2026-10-14" }, { "id": "dalco-registry", "title": "DALCO dapagliflozin trial registry", "url": "https://clinicaltrials.gov/study/NCT06907251", "type": "registry", "source_updated": "2026-07-01", "retrieved": "2026-10-15" }, { "id": "cdc-long-covid-care", "title": "CDC Long COVID clinical guidance", "url": "https://www.cdc.gov/long-covid/hcp/clinical-guidance/index.html", "type": "clinical_guidance", "retrieved": "2026-10-16" }, { "id": "cdc-pem-care", "title": "CDC ME/CFS activity-management guidance", "url": "https://www.cdc.gov/me-cfs/hcp/clinical-care/treating-the-most-disruptive-symptoms-first-and-preventing-worsening-of-symptoms.html", "type": "clinical_guidance", "retrieved": "2026-10-16" }, { "id": "modafinil-solriamfetol-registry", "title": "RECOVER-SLEEP Modafinil or solriamfetol registry", "url": "https://clinicaltrials.gov/study/NCT06404099", "type": "registry", "source_updated": "2026-06-03", "retrieved": "2026-10-16" }, { "id": "melatonin-light-registry", "title": "RECOVER-SLEEP Melatonin + light therapy registry", "url": "https://clinicaltrials.gov/study/NCT06404112", "type": "registry", "source_updated": "2026-07-08", "retrieved": "2026-10-16" } ], "interventions": [ { "id": "ensitrelvir", "name": "Ensitrelvir", "category": "Antiviral", "scope": "Established Long COVID", "evidence_label": "Randomized registry results available", "summary": "PREVAIL-LC has posted results from 40 participants. The posted primary outcome values alone do not establish a statistically reliable treatment benefit.", "summary_sources": [ "prevail-registry" ], "trials": [ "NCT06161688" ], "findings": [ { "outcome": "PROMIS-29 physical health summary at day 10", "population": "Adults with established Long COVID, single US centre", "comparator": "Placebo", "intervention_n": 20, "comparator_n": 20, "intervention_value": 43.6, "comparator_value": 41.6, "unit": "score", "intervention_ci95": [ 41.7, 45.4 ], "comparator_ci95": [ 39.7, 43.4 ], "contrast": { "estimate": null, "p_value": null, "ci95": null, "status": "Between-group confidence interval and p-value not supplied; no reconstructed inferential result." }, "interpretation": "Registry-reported baseline-adjusted day-10 arm means. The planned ANCOVA comparison adjusts for baseline; its between-group confidence interval and p-value are not posted.", "source_ids": [ "prevail-registry", "prevail-protocol-sap" ], "analysis_plan": { "method": "ANCOVA", "baseline_definition": "Mean of screening and baseline scores", "population": "Modified intention-to-treat: randomized participants who received study drug", "source_ids": [ "prevail-protocol-sap" ] } }, { "outcome": "Serious adverse events", "intervention_affected": 0, "intervention_at_risk": 20, "comparator_affected": 0, "comparator_at_risk": 20, "timepoint": "Up to two months", "interpretation": "Small sample; zero reported serious events does not establish safety.", "source_ids": [ "prevail-registry" ] } ], "limitations": [ "Small proof-of-concept trial; five-day regimen and short primary follow-up.", "The analysis plan is now checked, but a full results report and the primary between-group uncertainty estimate remain unverified.", "Generalizability to severe/housebound patients is not established by this pilot.", "The statistical analysis plan was finalized on 21 February 2025, after the registry's 20 December 2024 primary-completion date. Unblinding timing is unverified; these dates alone do not establish outcome switching." ], "access": { "canadian_marketing_status": "unverified", "long_covid_indication": "unverified", "coverage": "not_checked", "manufacturer_supply": "unverified", "text": "Canadian authorization, coverage and manufacturer-supported access have not been established in this pilot. SAP is a practitioner-requested process; drug-specific authorization and supply cannot be assumed.", "source_ids": [ "sap" ] }, "campaign_url": "https://longcovidaction.ca/ensitrelvir", "next_review": "Locate the full ANCOVA results and verify analysis-plan/unblinding chronology before an efficacy conclusion.", "source_checked": "2026-10-13" }, { "id": "obeldesivir", "name": "Obeldesivir", "category": "Antiviral", "scope": "Indirect evidence only", "evidence_label": "Acute-COVID results; no established Long COVID trial identified", "summary": "The identified randomized trials treated acute COVID-19. Their findings do not demonstrate benefit for people with established Long COVID.", "summary_sources": [ "oaktree-paper", "birch-paper" ], "trials": [ "NCT05715528", "NCT05603143" ], "findings": [ { "outcome": "Time to acute-COVID symptom alleviation", "trial_id": "NCT05715528", "timepoint": "By day 29", "median_days": [ 5.9, 6 ], "hazard_ratio": 1.099, "ci95": [ 0.997, 1.211 ], "p_value": 0.068, "interpretation": "Primary acute-COVID endpoint did not reach statistical significance; not a Long COVID treatment result.", "source_ids": [ "oaktree-paper", "oaktree-registry" ] }, { "outcome": "Acute-COVID hospitalization or all-cause death", "trial_id": "NCT05603143", "timepoint": "Day 29", "events": [ 0, 1 ], "denominators": [ 211, 207 ], "p_value": 0.32, "interpretation": "Sparse events and early stopping limit the acute-COVID conclusion; no established Long COVID population.", "source_ids": [ "birch-paper", "birch-registry" ] } ], "limitations": [ "An all-condition obeldesivir registry search returned six studies, none identified as treatment of established Long COVID. This is not a global proof of absence.", "Reduced viral measures during acute infection do not establish relief of established Long COVID.", "No direct Long COVID efficacy estimate is calculated." ], "access": { "canadian_marketing_status": "unverified", "long_covid_indication": "unverified", "coverage": "not_checked", "manufacturer_supply": "unverified", "text": "Gilead described obeldesivir as investigational in June 2026. A Canadian marketed product or manufacturer-supported Long COVID access route has not been verified. Acute-COVID trial authorization does not establish treatment availability.", "source_ids": [ "gilead-june-2026" ] }, "campaign_url": "https://longcovidaction.ca/obeldesivir", "next_review": "Verify Canadian authorization and manufacturer-supported Long COVID research or access; recheck registry aliases when new studies appear.", "source_checked": "2026-10-13" }, { "id": "ivabradine", "name": "Ivabradine", "category": "Symptom management", "scope": "Long COVID-associated POTS", "evidence_label": "Randomized conference results available; full report review pending", "summary": "In RECOVER-AUTONOMIC, ivabradine did not significantly improve the main orthostatic symptom score overall. It reduced the heart-rate rise on standing. Conference results also suggest the symptom effect differed by care assignment.", "summary_sources": [ "recover-acc-slides", "recover-announcement" ], "trials": [ "NCT06305806", "NCT05481177" ], "findings": [ { "outcome": "Orthostatic symptom questionnaire", "trial_id": "NCT06305806", "participants_total": 181, "timepoint": "Three months", "estimate": -0.14, "ci95": [ -0.72, 0.43 ], "p_value": 0.63, "interpretation": "No statistically significant overall symptom difference at three months. Lower scores favour ivabradine; this conference result does not establish equivalence.", "source_ids": [ "recover-acc-slides" ], "unit": "OHQ/OIQ points", "estimate_type": "Adjusted between-group difference in change", "intervention_n": 86, "comparator_n": 95 }, { "outcome": "Change in standing-minus-supine heart-rate rise", "trial_id": "NCT06305806", "interpretation": "The standing-related heart-rate rise decreased more with ivabradine. This physiological result is distinct from symptom improvement.", "source_ids": [ "recover-acc-slides" ], "estimate": -3.95, "ci95": [ -6.78, -1.12 ], "p_value": 0.007, "unit": "beats/minute", "estimate_type": "Adjusted between-group difference in change" }, { "outcome": "Symptoms after treatment", "report_id": "PMID37469536", "population": "COVID-associated POTS", "participants_total": 55, "reported_improved": 43, "timepoint": "Within seven days", "interpretation": "Uncontrolled observational study; reported improvement is not a placebo-adjusted treatment effect.", "source_ids": [ "iva-observational" ] }, { "outcome": "Treatment-by-care interaction in orthostatic symptoms", "trial_id": "NCT06305806", "analysis": "Prespecified factorial analysis, as described in conference slides", "interaction_p_value": 0.004, "strata": [ { "care": "Coordinated care", "contrast": "Ivabradine versus placebo", "estimate": -1.03, "ci95": [ -1.83, -0.23 ] }, { "care": "Usual care", "contrast": "Ivabradine versus placebo", "estimate": 0.72, "ci95": [ -0.09, 1.52 ] } ], "unit": "OHQ/OIQ points", "interpretation": "Care-stratum drug-versus-placebo comparisons; these are not a direct comparison of the two ivabradine groups. Full report review is pending.", "source_ids": [ "recover-acc-slides" ] } ], "limitations": [ "Numerical results are verified against investigator conference slides; a full peer-reviewed efficacy report was not identified in this scoped search.", "The care interaction should not replace the overall primary result or be described as proof of universal symptom benefit.", "COVIVA's 2025 publication is a protocol, not outcome evidence.", "The platform registry's posted results are enrolment totals; zero-denominator safety rows cannot be read as zero adverse events.", "Severe/housebound applicability and PEM-specific safety outcomes require further review.", "A complete comparative harms table has not been verified. Study completion is not a safety outcome." ], "access": { "canadian_marketing_status": "marketed_product_verified", "long_covid_indication": "not_listed_in_lancora_monograph", "coverage": "ontario_limited_use_heart_failure_verified; other_provinces_not_checked", "manufacturer_supply": "marketed_product_not_patient_supply_guarantee", "text": "Lancora is marketed in Canada for specified chronic heart failure; Long COVID/POTS is not a listed indication. Ontario limited-use code 538 applies to qualifying heart failure, not Long COVID/POTS alone. Other coverage routes and provinces remain unverified.", "source_ids": [ "lancora-dpd", "lancora-monograph", "ontario-iva-lu" ] }, "campaign_url": null, "next_review": "Reconcile the conference estimates and complete harms with a full efficacy report; obtain current COVIVA recruitment confirmation.", "source_checked": "2026-10-13" }, { "id": "paxlovid", "name": "Paxlovid", "aliases": [ "nirmatrelvir", "ritonavir" ], "category": "Antiviral", "scope": "Established Long COVID", "evidence_label": "Three published randomized trials; no significant primary benefit", "summary": "STOP-PASC, PAX LC and RECOVER-VITAL did not show statistically significant improvement on their primary Long COVID outcomes with the tested regimens. These findings concern established Long COVID, not treatment of a new acute infection.", "summary_sources": [ "stop-pasc-paper", "paxlc-paper", "vital-paper" ], "trials": [ "NCT05576662", "NCT05668091", "NCT05965726" ], "findings": [ { "outcome": "STOP-PASC: symptoms at 10 weeks", "interpretation": "A 15-day course did not significantly improve the pooled six-symptom primary outcome versus placebo plus ritonavir. The publication randomized 155 people; the registry count of 168 includes those who consented and were screened.", "source_ids": [ "stop-pasc-paper", "nct05576662" ], "trial_id": "NCT05576662", "participants_total": 155 }, { "outcome": "PAX LC: physical health at day 28", "interpretation": "Adjusted difference −0.55 PROMIS-29 points (95% CI −2.32 to 1.21; p=0.54), after 15 days of treatment. No significant primary benefit.", "source_ids": [ "paxlc-paper" ], "trial_id": "NCT05668091", "participants_total": 100, "estimate": -0.55, "ci95": [ -2.32, 1.21 ], "p_value": 0.54 }, { "outcome": "RECOVER-VITAL: symptoms at day 90", "interpretation": "The August 2026 publication reported no significant primary benefit with either 15 or 25 days in cognitive, autonomic or exercise/PEM phenotypes. For 25 days, adjusted differences in clinically significant improvement were 3.2 percentage points (95% CI −10.4 to 16.8), −6.4 (−18.5 to 5.7) and −7.8 (−19.5 to 3.8), respectively.", "source_ids": [ "vital-paper" ], "trial_id": "NCT05965726", "participants_total": 964, "modified_intention_to_treat_n": 959 }, { "outcome": "Reported harms", "interpretation": "PAX LC reported drug-related events in 35/46 treated participants versus 27/49 controls, commonly altered taste; no serious events through six weeks. RECOVER-VITAL Table 3 reports any adverse event in 212/323 (25-day), 204/320 (15-day) and 185/320 (placebo–ritonavir). Treatment-related serious events affected one participant per group. These descriptive counts do not establish equivalent safety.", "source_ids": [ "paxlc-paper", "vital-full" ], "safety_comparison": { "trial_id": "NCT05965726", "outcome": "Participants with any adverse event", "groups": [ { "arm": "Nirmatrelvir–ritonavir 25 days", "events": 212, "denominator": 323 }, { "arm": "Nirmatrelvir–ritonavir 15 days", "events": 204, "denominator": 320 }, { "arm": "Placebo–ritonavir 25 days", "events": 185, "denominator": 320 } ], "risk_differences_percentage_points": [ { "contrast": "25 days versus placebo–ritonavir", "estimate": 7.8, "ci95": [ 0.3, 15.3 ] }, { "contrast": "15 days versus placebo–ritonavir", "estimate": 5.9, "ci95": [ -1.6, 13.4 ] } ], "treatment_related_serious_events_participants": [ 1, 1, 1 ], "source_ids": [ "vital-full" ] } } ], "limitations": [ "Results concern the studied regimens and populations; they do not rule out every antiviral strategy or subgroup.", "Full-report review confirms that 31 participants belonged to multiple symptom clusters; the phenotype counts must not be summed as unique people. Table 3 supplies arm-level safety counts. Independent clinical interpretation remains pending.", "Acute treatment and prevention trials are excluded from the Canadian Long COVID treatment recruitment filter." ], "access": { "canadian_marketing_status": "acute_covid_authorization_verified", "long_covid_indication": "not_established_by_cited_authorization", "coverage": "not_checked", "manufacturer_supply": "not_checked", "text": "Health Canada authorized Paxlovid for acute COVID-19 in people at high risk of severe disease. That does not establish a Long COVID indication or coverage for extended courses. Important drug interactions require clinician/pharmacist review.", "source_ids": [ "pax-canada", "pax-interactions" ] }, "next_review": "Monitor corrections and new outcome or harms reports; independent clinical review can be added later.", "source_checked": "2026-10-13" }, { "id": "ldn", "name": "Low-dose naltrexone (LDN)", "aliases": [ "naltrexone" ], "category": "Immune-directed research", "scope": "Long COVID fatigue; selected ME/CFS overlap", "evidence_label": "Observational findings; randomized results pending", "summary": "A small retrospective study reported symptom improvements, but it cannot establish treatment benefit. The Canadian randomized trial is completed with no registry results posted; LIFT also studies LDN.", "summary_sources": [ "ldn-paper", "nct05430152", "nct06366724" ], "trials": [ "NCT05430152", "NCT06366724" ], "findings": [ { "outcome": "Retrospective symptom and function changes", "interpretation": "Among 59 people with paired questionnaires, LDN use was associated with improvements in fatigue, PEM, sleep and function. Composite symptom scores improved in 32 and worsened in 19. This selected, uncontrolled analysis cannot separate medication effects from other changes.", "source_ids": [ "ldn-paper" ], "participants_total": 59 }, { "outcome": "Canadian randomized evidence", "interpretation": "The BC trial enrolled 160 participants and completed in February 2026. Its primary outcome measures fatigue at 16 weeks. No registry results were posted when checked; completion and the published protocol are not outcome evidence.", "source_ids": [ "nct05430152" ], "trial_id": "NCT05430152", "participants_total": 160 }, { "outcome": "LIFT: shared trial with pyridostigmine", "interpretation": "One four-arm trial tests LDN, pyridostigmine, their combination and placebo in ME/CFS with orthostatic intolerance, including eligible Long COVID patients. No results posted. The planned 160 participants are shared across the trial. An August 2026 peer-reviewed protocol describes the study design, not treatment results or confirmed current recruitment.", "source_ids": [ "nct06366724", "lift-protocol" ], "trial_id": "NCT06366724" } ], "limitations": [ "Observational findings are vulnerable to selection bias, missing follow-up and confounding.", "LIFT’s population is narrower than Long COVID as a whole.", "Comprehensive comparative harms and formal certainty assessment are pending." ], "access": { "canadian_marketing_status": "not_verified_in_this_review", "long_covid_indication": "not_verified_in_this_review", "coverage": "not_checked", "manufacturer_supply": "not_checked", "text": "The BC trial used compounded low-dose capsules and is completed. Routine Canadian access, compounding costs and coverage are unverified. LIFT is based in Boston; Canadian participation is not established.", "source_ids": [ "nct05430152", "nct06366724" ] }, "next_review": "Check for BC trial results and obtain a current LIFT recruitment update; assess randomized harms alongside benefit.", "source_checked": "2026-10-13" }, { "id": "ivig", "name": "Intravenous immunoglobulin (IVIG)", "aliases": [ "immunoglobulin" ], "category": "Immune-directed research", "scope": "Selected neurological and autonomic Long COVID", "evidence_label": "Small observational signal; randomized results pending", "summary": "A small nonrandomized study reported improvement in post-COVID small-fibre neuropathy. RECOVER-AUTONOMIC’s IVIG trial is completed with no posted results. An NIH neurological study enrols by invitation.", "summary_sources": [ "ivig-paper", "nct06305793", "nct05350774" ], "trials": [ "NCT06305793", "NCT05350774" ], "findings": [ { "outcome": "Small-fibre neuropathy case-control study", "interpretation": "Neuropathic symptom response was reported in 9/9 IVIG-treated patients versus 3/7 untreated patients (p=0.02). This small retrospective, nonrandomized comparison cannot establish efficacy for Long COVID broadly.", "source_ids": [ "ivig-paper" ], "participants_total": 16 }, { "outcome": "RECOVER-AUTONOMIC IVIG", "interpretation": "The randomized IVIG appendix enrolled 200 people and completed in June 2026. No results posted when checked. The shared platform’s enrolment totals are not efficacy or usable comparative safety findings.", "source_ids": [ "nct06305793", "recover-platform" ], "trial_id": "NCT06305793", "participants_total": 200 }, { "outcome": "NIH neurological trial", "interpretation": "The registry lists enrolment by invitation with 45 planned participants and requires prior study participation. It is not an open Canadian recruitment opportunity. No results posted.", "source_ids": [ "nct05350774" ], "trial_id": "NCT05350774" } ], "limitations": [ "Biopsy-confirmed small-fibre neuropathy and selected trial populations do not represent all Long COVID.", "An observational response comparison is not a randomized treatment effect.", "Full comparative harms are pending; absent results do not establish safety." ], "access": { "canadian_marketing_status": "not_verified_in_this_review", "long_covid_indication": "not_verified_in_this_review", "coverage": "not_checked", "manufacturer_supply": "not_checked", "text": "No Canadian site is listed in these two selected trials. Routine Canadian eligibility, product access and provincial funding for Long COVID are not established in this review.", "source_ids": [ "nct06305793", "nct05350774" ] }, "next_review": "Check for RECOVER IVIG results and assess efficacy, adverse events and subgroup applicability together.", "source_checked": "2026-10-13" }, { "id": "pyridostigmine", "name": "Pyridostigmine", "aliases": [ "Mestinon" ], "category": "Symptom management", "scope": "ME/CFS with orthostatic intolerance, including eligible Long COVID", "evidence_label": "Trial listed as recruiting; current availability unconfirmed", "summary": "LIFT tests pyridostigmine alone and with LDN in people with ME/CFS and orthostatic intolerance, including qualifying Long COVID patients. No results are posted. Current recruitment needs confirmation.", "summary_sources": [ "nct06366724" ], "trials": [ "NCT06366724" ], "findings": [ { "outcome": "LIFT factorial trial", "interpretation": "The planned 160-person, four-arm trial measures function and exercise-related physiology. It is shared with the LDN entry, not a second independent trial. Registry status says recruiting, but its October 2025 update is old and estimated primary completion has passed. An August 2026 peer-reviewed protocol describes the study design, not treatment results or confirmed current recruitment.", "source_ids": [ "nct06366724", "lift-protocol" ], "trial_id": "NCT06366724" } ], "limitations": [ "Trial registration cannot establish benefit.", "Eligibility requires ME/CFS and orthostatic intolerance; applicability to all Long COVID is uncertain.", "Exercise testing and travel may limit participation for people with PEM or severe illness." ], "access": { "canadian_marketing_status": "not_verified_in_this_review", "long_covid_indication": "not_verified_in_this_review", "coverage": "not_checked", "manufacturer_supply": "not_checked", "text": "LIFT is based in Boston with no Canadian site listed. Cross-border eligibility, routine Canadian prescribing access and coverage are not verified here.", "source_ids": [ "nct06366724" ] }, "next_review": "Confirm whether LIFT is accepting participants and check for results; count this shared trial once.", "source_checked": "2026-10-13" }, { "id": "upadacitinib", "name": "Upadacitinib", "aliases": [ "Rinvoq" ], "category": "Immune-directed research", "scope": "Established Long COVID", "evidence_label": "Canadian sites listed as recruiting; no results posted", "summary": "LC-REVITALIZE tests upadacitinib and pirfenidone against matched placebo. Its registry lists recruiting sites in Montreal and Sherbrooke. No results are posted; availability of the upadacitinib arm needs confirmation.", "summary_sources": [ "nct06928272" ], "trials": [ "NCT06928272" ], "findings": [ { "outcome": "LC-REVITALIZE platform", "interpretation": "The initial phase plans 348 participants across two drugs and placebo groups. The primary outcome tracks the worst baseline symptom domain during follow-up; the registry specifies enrolment through month six. This is not an upadacitinib-only sample, and authorization to run a trial is not evidence of benefit.", "source_ids": [ "nct06928272", "revitalize-canada" ], "trial_id": "NCT06928272" } ], "limitations": [ "No randomized efficacy or safety results posted when checked.", "Eligibility criteria and exclusions limit who can participate.", "A recruiting site listing does not guarantee an open local drug arm, eligibility or enrolment." ], "access": { "canadian_marketing_status": "not_verified_in_this_review", "long_covid_indication": "investigational_trial_use; routine_indication_not_verified", "coverage": "not_checked", "manufacturer_supply": "not_checked", "text": "Health Canada lists an authorized LC-REVITALIZE trial. ClinicalTrials.gov lists IRCM in Montreal and CRCHUS in Sherbrooke as recruiting (updated 6 October 2026). Confirm the site, eligibility and upadacitinib arm with the study team. Routine Long COVID access and coverage are not established. Recherche Santé Québec also lists these locations as open but identifies ClinicalTrials.gov as its data source; this is not independent site confirmation.", "source_ids": [ "nct06928272", "revitalize-canada", "revitalize-quebec" ] }, "next_review": "Confirm Canadian site and drug-arm availability; monitor registry changes and first results.", "source_checked": "2026-10-13" }, { "id": "famotidine-loratadine", "name": "Famotidine + loratadine", "aliases": [ "H1 H2 antihistamines", "STIMULATE-ICP" ], "category": "Symptom management", "scope": "Established Long COVID fatigue", "evidence_label": "Randomized results; small short-term difference", "summary": "The tested antihistamine combination produced a small additional fatigue-score improvement at 12 weeks. The difference was not sustained at 24 weeks, and sensitivity analyses weakened confidence in the finding.", "summary_sources": [ "stimulate-drug-paper" ], "trials": [ "ISRCTN10665760" ], "findings": [ { "outcome": "Fatigue at 12 weeks", "interpretation": "Adjusted difference versus no study drug: −1.48 FAS points (95% CI −2.88 to −0.08). Lower scores mean less fatigue; a statistically detectable difference is not necessarily a meaningful improvement.", "source_ids": [ "stimulate-drug-paper" ], "trial_id": "ISRCTN10665760", "contrast": { "estimate": -1.48, "ci95": [ -2.88, -0.08 ], "p_value": 0.038, "measure": "Adjusted FAS mean difference", "timepoint": "12 weeks" } }, { "outcome": "Reported adverse events", "interpretation": "51/193 participants in the combination group versus 21/196 receiving no study drug reported an adverse event. Open-label reporting and the sample size limit safety conclusions.", "source_ids": [ "stimulate-drug-paper" ], "trial_id": "ISRCTN10665760" } ], "limitations": [ "Open-label study with self-reported fatigue; expectations and missing data can affect estimates.", "Sensitivity analyses addressing missing data or full treatment completion did not retain statistical significance for the small colchicine and antihistamine differences.", "No sustained between-group fatigue difference at 24 weeks. This does not establish a cure or benefit for every Long COVID symptom.", "This trial tested famotidine and loratadine together. It cannot establish either component's independent effect or benefit from all antihistamines." ], "access": { "canadian_marketing_status": "not_verified_in_this_review", "long_covid_indication": "not_verified_in_this_review", "coverage": "not_checked", "manufacturer_supply": "not_checked", "text": "Canadian authorization for this use, supply, cost and coverage were not verified in this update. Availability for another condition would not establish benefit for Long COVID.", "source_ids": [] }, "next_review": "Check subsequent trials, corrections and longer-term results; assess Canadian access separately.", "source_checked": "2026-10-14" }, { "id": "colchicine", "name": "Colchicine", "aliases": [ "STIMULATE-ICP" ], "category": "Immune-directed research", "scope": "Established Long COVID", "evidence_label": "Randomized results differ by outcome and timepoint", "summary": "A UK trial found a small, short-term fatigue difference. A separate placebo-controlled trial in India did not demonstrate better walking-distance improvement at 52 weeks. These findings do not establish a broadly effective treatment.", "summary_sources": [ "stimulate-drug-paper", "colchicine-india-paper" ], "trials": [ "ISRCTN10665760", "CTRI/2021/11/038234" ], "findings": [ { "outcome": "STIMULATE-ICP: fatigue at 12 weeks", "interpretation": "Adjusted difference versus no study drug: −1.49 FAS points (95% CI −2.92 to −0.06). The difference was not sustained at 24 weeks.", "source_ids": [ "stimulate-drug-paper" ], "trial_id": "ISRCTN10665760", "contrast": { "estimate": -1.49, "ci95": [ -2.92, -0.06 ], "p_value": 0.041, "measure": "Adjusted FAS mean difference", "timepoint": "12 weeks" } }, { "outcome": "India: walking-distance change at 52 weeks", "interpretation": "Difference: 5.59 metres (95% CI −9.00 to 20.18), after 26 weeks of treatment. The trial randomized 350 people; the primary outcome model included 319.", "source_ids": [ "colchicine-india-paper" ], "trial_id": "CTRI/2021/11/038234", "participants_total": 350, "analysis_n": 319, "contrast": { "estimate": 5.59, "ci95": [ -9, 20.18 ], "p_value": 0.45, "measure": "Adjusted difference in 6-minute walk distance change, metres", "timepoint": "52 weeks" } }, { "outcome": "Reported harms", "interpretation": "In STIMULATE-ICP, 57/192 versus 21/196 reported adverse events; 27 colchicine participants had gastrointestinal events. In India, adverse events were reported by 35/176 versus 30/170, and medication was stopped because of events by 3 versus 1. Two deaths occurred in the colchicine group (suicide and miliary tuberculosis); these counts alone do not establish drug causation.", "source_ids": [ "stimulate-drug-paper", "colchicine-india-paper" ] } ], "limitations": [ "Open-label study with self-reported fatigue; expectations and missing data can affect estimates.", "Sensitivity analyses addressing missing data or full treatment completion did not retain statistical significance for the small colchicine and antihistamine differences.", "No sustained between-group fatigue difference at 24 weeks. This does not establish a cure or benefit for every Long COVID symptom.", "The trials used different regimens, populations, comparators and outcomes; their estimates should not be pooled casually.", "The Indian study permitted enrollment from 22 days after infection, although the median interval was much longer. The report uses 346 for the treated population and 319 for the primary outcome analysis." ], "access": { "canadian_marketing_status": "not_verified_in_this_review", "long_covid_indication": "not_verified_in_this_review", "coverage": "not_checked", "manufacturer_supply": "not_checked", "text": "Canadian authorization for this use, supply, cost and coverage were not verified in this update. Availability for another condition would not establish benefit for Long COVID.", "source_ids": [] }, "next_review": "Check further randomized reports and corrections; retain distinct fatigue and functional outcomes.", "source_checked": "2026-10-14" }, { "id": "rivaroxaban", "name": "Rivaroxaban", "aliases": [ "anticoagulant", "STIMULATE-ICP" ], "category": "Anticoagulant research", "scope": "Established Long COVID fatigue", "evidence_label": "Randomized trial did not demonstrate primary-outcome benefit", "summary": "STIMULATE-ICP did not demonstrate a fatigue benefit over no study drug at 12 weeks. Bleeding events were reported. This trial does not support a general claim that anticoagulation treats Long COVID.", "summary_sources": [ "stimulate-drug-paper" ], "trials": [ "ISRCTN10665760" ], "findings": [ { "outcome": "Fatigue at 12 weeks", "interpretation": "Adjusted difference: −1.06 FAS points (95% CI −2.47 to 0.35); the interval includes no difference. No between-group fatigue difference was demonstrated at 24 weeks.", "source_ids": [ "stimulate-drug-paper" ], "trial_id": "ISRCTN10665760", "contrast": { "estimate": -1.06, "ci95": [ -2.47, 0.35 ], "p_value": 0.139, "measure": "Adjusted FAS mean difference", "timepoint": "12 weeks" } }, { "outcome": "Reported harms", "interpretation": "70/197 participants versus 21/196 receiving no study drug reported adverse events. Minor bleeding or heavy menstrual bleeding was reported in 26/197 rivaroxaban participants. Five serious events in three rivaroxaban participants were judged unrelated to the study drug by investigators.", "source_ids": [ "stimulate-drug-paper" ], "trial_id": "ISRCTN10665760" } ], "limitations": [ "Open-label trial; fatigue and adverse-event reporting can be affected by knowledge of treatment.", "A confidence interval crossing zero does not prove every possible regimen has no effect.", "This is one rivaroxaban regimen, not evidence about every anticoagulant or treatment combination." ], "access": { "canadian_marketing_status": "not_verified_in_this_review", "long_covid_indication": "not_verified_in_this_review", "coverage": "not_checked", "manufacturer_supply": "not_checked", "text": "Canadian authorization for this use, supply, cost and coverage were not verified in this update. Availability for another condition would not establish benefit for Long COVID.", "source_ids": [] }, "next_review": "Check new controlled trials and harms; keep claims specific to the tested regimen and outcome.", "source_checked": "2026-10-14" }, { "id": "hbot", "name": "Hyperbaric oxygen therapy (HBOT)", "aliases": [ "oxygen therapy", "RECLAIM", "HOT-LoCO", "brain fog" ], "category": "Oxygen therapy", "scope": "Established Long COVID", "evidence_label": "Mixed randomized findings; protocols differ", "summary": "A 40-session trial reported short-term cognitive improvement. Two later 10-session trials did not demonstrate benefit on their main comparisons. Different protocols and outcomes prevent a simple conclusion that more sessions work better.", "summary_sources": [ "hbot-israel-paper", "hbot-hotloco-paper", "hbot-belgium-paper" ], "trials": [ "NCT04647656", "NCT04842448", "HBOT-BELGIUM-2025", "NCT06452095", "NCT06082518" ], "findings": [ { "outcome": "40 sessions: cognitive outcome", "interpretation": "The 2022 trial reported a group-by-time difference in global cognition (effect size d=0.495; p=0.038), assessed 1–3 weeks after treatment. Its Results section reports 79 randomized and 73 analyzed.", "source_ids": [ "hbot-israel-paper" ], "trial_id": "NCT04647656", "participants_total": 79, "analysis_n": 73 }, { "outcome": "10 sessions: HOT-LoCO", "interpretation": "Among 80 randomized participants, the 13-week between-group differences were 0.63 points for physical functioning (95% CI −7.04 to 8.29) and 2.35 for physical role limitations (−5.95 to 10.66). Neither primary comparison demonstrated benefit.", "source_ids": [ "hbot-hotloco-paper" ], "trial_id": "NCT04842448", "participants_total": 80, "analysis_n": 79 }, { "outcome": "10 sessions: Belgian four-group trial", "interpretation": "101 participants were randomized to different oxygen/pressure conditions. No significant between-group differences in symptoms, function or cognitive performance were reported after treatment.", "source_ids": [ "hbot-belgium-paper" ], "trial_id": "HBOT-BELGIUM-2025", "participants_total": 101 }, { "outcome": "Reported harms and burden", "interpretation": "The 2022 report recorded side effects in 35.1% of HBOT and 38.9% of control participants. HOT-LoCO reported adverse events in 19 HBOT and 18 placebo participants, including a seizure judged probably related to HBOT and a placebo-group death judged unrelated. Four Belgian-trial participants stopped because of middle-ear pressure injury. These findings do not establish that HBOT is safe for everyone.", "source_ids": [ "hbot-israel-paper", "hbot-hotloco-paper", "hbot-belgium-paper" ] } ], "limitations": [ "Small studies, differing oxygen pressures, sham procedures, populations and outcomes limit comparison.", "The 2022 abstract and Results section differ on the randomized count; this summary uses the Results section and keeps analyzed participants separate.", "Short-term results do not establish durable benefit. The 2022 authors disclosed commercial relationships with AVIV Scientific.", "Repeated chamber visits and testing can be burdensome. Applicability to severe, housebound or PEM-affected patients needs assessment.", "HOT-LoCO also reported a later secondary responder finding at 52 weeks; this is distinct from its negative primary 13-week comparisons and requires cautious interpretation." ], "access": { "canadian_marketing_status": "not_verified_in_this_review", "long_covid_indication": "not_verified_in_this_review", "coverage": "not_checked", "manufacturer_supply": "not_checked", "text": "The Canadian directory lists RECLAIM HBOT at UHN in Toronto as recruiting and the Sunnybrook study as ongoing without recruitment (registry checks: 13 October 2026). Confirm openings, visits, eligibility and accommodations with the team. Routine Canadian coverage and treatment costs were not verified.", "source_ids": [ "reclaim-hbot-registry", "sunnybrook-hbot-registry", "reclaim-interventions" ] }, "next_review": "Monitor Canadian trial results and recruitment; check long-term controlled outcomes and protocol-specific harms.", "source_checked": "2026-10-14" }, { "id": "taurine", "name": "Taurine", "aliases": [ "TaurineLC", "TaurineLCPeds", "RECLAIM taurine" ], "category": "Supplement research", "scope": "Established Long COVID; adult and adolescent studies", "evidence_label": "Biomarker association; treatment results pending", "summary": "Blood taurine levels have been associated with symptom burden, but this does not show that taking taurine improves Long COVID. Canadian adult and adolescent studies are testing different questions; neither registry has posted results.", "summary_sources": [ "taurine-biomarker", "nct06721949", "nct07682402" ], "trials": [ "NCT06721949", "NCT07682402" ], "findings": [ { "outcome": "Observational biomarker evidence", "interpretation": "A study of 117 people initially hospitalized with COVID-19, with 28 healthy controls, linked taurine trajectories to later symptoms and outcomes. It did not randomize people to taurine supplements, so its associations cannot establish treatment benefit.", "source_ids": [ "taurine-biomarker" ] }, { "outcome": "Adult randomized trial", "interpretation": "TaurineLC plans 300 participants. Primary outcomes assess fatigue and cognitive performance at three months. No registry results were posted when checked.", "source_ids": [ "nct06721949" ], "trial_id": "NCT06721949" }, { "outcome": "Adolescent study", "interpretation": "TaurineLCPeds plans 30 participants aged 10–17 in a single-group, open-label study. The primary outcome is blood taurine change at three months; this is different from demonstrating symptom benefit versus placebo.", "source_ids": [ "nct07682402" ], "trial_id": "NCT07682402" }, { "outcome": "Safety evidence", "interpretation": "The biomarker study does not establish supplement safety. Comparative Long COVID harms results from these Canadian studies are not yet available in their registry records.", "source_ids": [ "taurine-biomarker", "nct06721949", "nct07682402" ] } ], "limitations": [ "Association does not establish that a deficiency causes symptoms or that supplementation reverses them.", "Findings from adults initially hospitalized with COVID-19 may not apply to all Long COVID populations.", "The adolescent study has no placebo group. Blood-level change is not equivalent to clinical improvement." ], "access": { "canadian_marketing_status": "not_verified_in_this_review", "long_covid_indication": "not_verified_in_this_review", "coverage": "not_checked", "manufacturer_supply": "not_checked", "text": "The adult trial lists recruiting sites in Alberta, British Columbia, Ontario and Quebec. The adolescent registry says not yet recruiting, has no posted sites and retains an estimated September 2026 start date that has passed. Confirm openings and eligibility with the team. Retail availability does not establish Long COVID benefit; Canadian product authorization and coverage were not assessed.", "source_ids": [ "nct06721949", "nct07682402" ] }, "next_review": "Check adult randomized results and the adolescent opening date/site list; assess symptom outcomes and harms separately from taurine blood levels.", "source_checked": "2026-10-14" }, { "id": "pirfenidone", "name": "Pirfenidone", "aliases": [ "LC-REVITALIZE", "FIBRO-COVID" ], "category": "Antifibrotic research", "scope": "Long COVID research; separate post-pneumonia lung-fibrosis evidence", "evidence_label": "Related-condition randomized results; Long COVID platform results pending", "summary": "A trial after severe COVID-19 pneumonia did not demonstrate better lung recovery with pirfenidone than placebo. That population differs from Long COVID more broadly. LC-REVITALIZE is testing symptom outcomes and has no posted registry results.", "summary_sources": [ "pirfenidone-fibro", "nct06928272" ], "trials": [ "NCT04607928", "NCT06928272" ], "findings": [ { "outcome": "FIBRO-COVID: primary outcome", "interpretation": "Of 113 randomized participants, 103 were analyzed. At 24 weeks, the composite improvement outcome occurred in 79.7% receiving pirfenidone and 82.3% receiving placebo. The trial did not demonstrate superiority.", "source_ids": [ "pirfenidone-fibro" ], "trial_id": "NCT04607928", "participants_total": 113, "analysis_n": 103 }, { "outcome": "Reported harms", "interpretation": "Four pirfenidone participants and three placebo participants stopped because of toxicity. The report described similar adverse-event and hospitalization rates and no deaths. This does not establish safety for every patient.", "source_ids": [ "pirfenidone-fibro" ], "trial_id": "NCT04607928" }, { "outcome": "LC-REVITALIZE", "interpretation": "The planned 348 participants span upadacitinib, pirfenidone and matched placebo groups. This is one shared platform, not 348 people receiving pirfenidone. No registry results were posted when checked.", "source_ids": [ "nct06928272" ], "trial_id": "NCT06928272" } ], "limitations": [ "FIBRO-COVID enrolled people with CT lung changes after severe hospitalized pneumonia, 30–90 days after recovery/discharge; it is not a general Long COVID fatigue or brain-fog trial.", "Most participants were also receiving low-dose prednisone. Improvement within both groups does not establish a drug effect.", "The 2026 correction adds an author affiliation; it does not change the reported outcomes." ], "access": { "canadian_marketing_status": "not_verified_in_this_review", "long_covid_indication": "not_verified_in_this_review", "coverage": "not_checked", "manufacturer_supply": "not_checked", "text": "LC-REVITALIZE lists Montreal and Sherbrooke as recruiting. Confirm whether the pirfenidone arm is available locally. Authorization to run a study does not establish treatment benefit or routine Long COVID access; coverage and supply were not verified.", "source_ids": [ "nct06928272" ] }, "next_review": "Check LC-REVITALIZE arm-specific results and Canadian availability; retain the distinction between lung-fibrosis and broader Long COVID outcomes.", "source_checked": "2026-10-14" }, { "id": "hioxsr", "name": "Hi-OxSR breathing device", "aliases": [ "HiOxSR", "Hi-Ox", "RECLAIM HiOxSR", "carbon dioxide rebreathing" ], "category": "Oxygen therapy", "scope": "Post-COVID cognitive symptoms", "evidence_label": "Uncontrolled pilot abstract; randomized results pending", "summary": "A small open-label pilot reported cognitive and symptom improvements, but without a control group it cannot establish benefit. A Canadian randomized study is testing the device; no results are posted in its registry.", "summary_sources": [ "hiox-pilot-abstract", "nct06928506" ], "trials": [ "NCT06928506" ], "findings": [ { "outcome": "Pilot report", "interpretation": "The abstract reports 36 completers with improvements after device use. Repeat testing, expectations, natural changes and selection could contribute. This is a brief abstract hosted by the manufacturer, not a fully assessed randomized report.", "source_ids": [ "hiox-pilot-abstract" ], "completers_n": 36 }, { "outcome": "Reported pilot harms", "interpretation": "The abstract reports shortness of breath, nausea and headaches, with no severe adverse effects reported. A small uncontrolled study cannot establish safety or reliably detect uncommon harms.", "source_ids": [ "hiox-pilot-abstract" ] }, { "outcome": "Canadian randomized study", "interpretation": "The planned 120 participants are divided among three groups testing device-use duration and oxygen/rebreathing conditions. Primary cognitive tests are assessed through two months. No registry results were posted when checked.", "source_ids": [ "nct06928506" ], "trial_id": "NCT06928506" } ], "limitations": [ "The pilot's claims of safety and effectiveness exceed what an uncontrolled abstract can establish.", "The registry describes participants as knowing group allocation while being masked to the study hypothesis; this should not be presented as a fully blinded trial.", "Hi-OxSR is distinct from hyperbaric oxygen. Findings from HBOT cannot be transferred to this device." ], "access": { "canadian_marketing_status": "not_verified_in_this_review", "long_covid_indication": "not_verified_in_this_review", "coverage": "not_checked", "manufacturer_supply": "not_checked", "text": "The registry lists UHN Toronto as recruiting, while Edmonton and Sherbrooke remain not yet recruiting in the older record. RECLAIM's website lists enrollment open; confirm the specific site. Routine device access, cost and coverage were not verified.", "source_ids": [ "nct06928506", "reclaim-interventions" ] }, "next_review": "Seek a full pilot report and randomized outcomes; reconcile site openings and assess device-specific harms and participation burden.", "source_checked": "2026-10-14" }, { "id": "sgb", "name": "Stellate ganglion block (SGB)", "aliases": [ "stellate", "cervicothoracic sympathetic block", "STAR-CO", "parosmia" ], "category": "Procedure research", "scope": "Post-COVID smell distortion; broader Long COVID studies", "evidence_label": "Parosmia randomized trial negative; broader symptom evidence uncontrolled", "summary": "A placebo-controlled trial did not demonstrate benefit for persistent post-COVID smell distortion. Uncontrolled studies report broader symptom improvements but cannot establish causation. Canadian trials are testing symptom and functional outcomes.", "summary_sources": [ "sgb-parosmia", "sgb-cohort", "nct07374562", "nct07468604" ], "trials": [ "NCT06253806", "NCT07374562", "NCT07468604" ], "findings": [ { "outcome": "Randomized parosmia trial", "interpretation": "At three months, 13/30 SGB participants and 6/16 placebo participants met the prespecified response threshold. The study did not demonstrate superiority. This finding concerns smell distortion and the tested procedure, not every Long COVID symptom or block regimen.", "source_ids": [ "sgb-parosmia" ], "trial_id": "NCT06253806", "response": { "intervention_events": 13, "intervention_n": 30, "comparator_events": 6, "comparator_n": 16, "timepoint": "3 months" } }, { "outcome": "Broader symptoms: retrospective cohort", "interpretation": "A survey-based study of 52 patients reported improvements after treatment. There was no untreated or placebo comparison, and recall and selection bias limit causal interpretation.", "source_ids": [ "sgb-cohort" ], "participants_total": 52 }, { "outcome": "Reported harms", "interpretation": "The randomized trial reported transient hoarseness, congestion, headache and dizziness, with no serious or unexpected events reported. In the retrospective cohort, 13/52 reported adverse effects, including worsened post-exertional malaise; reported duration ranged from hours to months.", "source_ids": [ "sgb-parosmia", "sgb-cohort" ] }, { "outcome": "Canadian studies", "interpretation": "STAR-CO in Trois-Rivières and a Toronto cervicothoracic sympathetic block trial have no posted registry results. Their protocols and symptom targets differ from the published parosmia trial.", "source_ids": [ "nct07374562", "nct07468604" ] } ], "limitations": [ "Small, symptom-specific randomized evidence cannot settle effectiveness for every Long COVID presentation.", "Uncontrolled improvement does not separate treatment effects from other changes.", "The parosmia paper's abstract and Table 2 differ in the reported response-difference confidence interval. This summary reports the Table 2 counts and does not reproduce a disputed contrast.", "No serious event reported in a small trial is not proof that an invasive procedure is risk-free." ], "access": { "canadian_marketing_status": "not_verified_in_this_review", "long_covid_indication": "not_verified_in_this_review", "coverage": "not_checked", "manufacturer_supply": "not_checked", "text": "STAR-CO lists Trois-Rivières as recruiting. The Toronto registry lists Toronto Western recruiting and Women's College not yet recruiting. Confirm the site, protocol, eligibility and procedural risks with the study team. Routine Long COVID access and coverage were not verified.", "source_ids": [ "nct07374562", "nct07468604" ] }, "next_review": "Monitor Canadian randomized outcomes and harms; reconcile the parosmia report's numerical discrepancy before adding a confidence-interval estimate.", "source_checked": "2026-10-14" }, { "id": "guanfacine-nac", "name": "Guanfacine + N-acetylcysteine (NAC)", "aliases": [ "guanfacine", "NAC", "N-acetyl cysteine", "Intuniv", "brain fog", "cognition" ], "category": "Symptom management", "scope": "Cognitive symptoms in established Long COVID", "evidence_label": "Uncontrolled reports; benefit remains uncertain", "summary": "A small uncontrolled report described cognitive improvements with guanfacine plus NAC. It does not establish that the combination caused the improvement. Low blood pressure and dizziness led some patients to stop treatment.", "summary_sources": [ "guanfacine-nac-series" ], "trials": [], "findings": [ { "outcome": "Combination: 12-patient case series", "interpretation": "Eight of 12 patients reported cognitive improvement. Four discontinued: two for unspecified reasons and two because of low blood pressure and/or dizziness. There was no control group or blinded assessment.", "participants_total": 12, "reported_improvement_n": 8, "discontinued_total": 4, "discontinued_adverse_effects": 2, "discontinued_unspecified": 2, "source_ids": [ "guanfacine-nac-series" ] }, { "outcome": "Guanfacine alone: separate case report", "interpretation": "A 2024 report described improved symptoms and cognitive test performance in one patient over six months. NAC was not part of that treatment. This is not confirmation of the combination or evidence of an average treatment effect.", "participants_total": 1, "combination": false, "source_ids": [ "guanfacine-case" ] }, { "outcome": "Patient survey: research context", "interpretation": "A 2025 ME/CFS and Long COVID survey included the combination. Self-selected, retrospective treatment experiences can inform research questions but do not establish efficacy; concurrent treatments, recall and selection bias limit interpretation.", "source_ids": [ "guanfacine-survey" ] } ], "limitations": [ "Eight reported improvements out of 12 is not a reliable success rate for future patients. Without a comparison group, natural changes, expectations and other treatments cannot be separated from a drug effect.", "The case series does not isolate the contribution of guanfacine from NAC. The separate guanfacine-only case must not be pooled as another combination recipient.", "These small reports cannot establish safety, lasting benefit, or applicability to people with severe disease or post-exertional malaise.", "No controlled trial of this combination for Long COVID cognition was identified in the recorded search. This targeted search is not proof that none exists." ], "access": { "canadian_marketing_status": "not_verified_in_this_review", "long_covid_indication": "not_verified_in_this_review", "coverage": "not_checked", "manufacturer_supply": "not_checked", "text": "No Canadian trial of this combination was identified in this targeted registry search. Canadian authorization for this use, availability and coverage have not been verified. This entry provides no dosing or prescribing instructions.", "source_ids": [ "guanfacine-registry-search", "guanfacine-all-search" ] }, "next_review": "Check for controlled cognitive-outcome studies, comparative harms and Canadian access information. Keep guanfacine-only and combination findings separate.", "source_checked": "2026-10-14" }, { "id": "dapagliflozin", "name": "Dapagliflozin", "aliases": [ "DALCO", "SGLT2 inhibitor" ], "category": "Metabolic research", "scope": "Planned trial in established Long COVID", "evidence_label": "Upcoming Canadian trial; no posted registry results", "summary": "The planned Canadian DALCO trial will compare dapagliflozin with placebo in adults with Long COVID. The registry still says not yet recruiting and has no posted results; it does not establish a Long COVID treatment benefit.", "summary_sources": [ "dalco-registry" ], "trials": [ "NCT06907251" ], "findings": [ { "outcome": "Planned randomized comparison", "interpretation": "The registry plans 192 participants, with dapagliflozin or placebo over 12 months. Its primary outcome is the six-month change in an EQ-5D-derived health utility score. These are design details, not results.", "source_ids": [ "dalco-registry" ] }, { "outcome": "Recruitment and evidence status", "interpretation": "The record remained not yet recruiting when checked on 15 October 2026. The estimated September 2026 start date has passed, but an estimated date does not establish that recruitment opened. No results are posted in this registry record.", "source_ids": [ "dalco-registry" ] } ], "limitations": [ "This entry describes one registered planned study, not a completed evidence review of all dapagliflozin research.", "There are no posted trial outcome or adverse-event results to interpret. Absence of results is not evidence of safety or benefit.", "The study excludes several groups, including people with diabetes, prior heart failure or severe renal impairment. Applicability outside the eligibility criteria cannot be assumed." ], "access": { "text": "The University of Ottawa Heart Institute is the listed Canadian site. Confirm recruitment with the study team. This trial listing does not establish approval for Long COVID, coverage or routine treatment access.", "source_ids": [ "dalco-registry" ] }, "next_review": "Check for recruitment updates and posted or published outcomes. Review comparative benefit and harms before drawing a treatment conclusion.", "source_checked": "2026-10-15" }, { "id": "modafinil-solriamfetol", "name": "Modafinil or solriamfetol", "aliases": [ "RECOVER-SLEEP", "hypersomnia", "daytime sleepiness" ], "category": "Symptom management", "scope": "Sleep symptoms after COVID", "evidence_label": "Completed trial; no posted registry results", "summary": "RECOVER-SLEEP tested wakefulness medicines for excessive daytime sleepiness after COVID. The trial is completed, but its registry has no posted results. Long COVID benefit remains unestablished.", "summary_sources": [ "modafinil-solriamfetol-registry" ], "trials": [ "NCT06404099" ], "findings": [ { "outcome": "Study design", "interpretation": "Participants received modafinil or placebo; people unable to take modafinil could receive solriamfetol or placebo. The medicines form one wakefulness-treatment comparison, not two independent trials.", "source_ids": [ "modafinil-solriamfetol-registry" ] }, { "outcome": "Results and harms", "interpretation": "No results are posted in this registry record as of 16 October 2026. Completion and enrolment counts are not evidence of benefit or safety.", "source_ids": [ "modafinil-solriamfetol-registry" ] } ], "limitations": [ "This is a scoped registry summary, not an exhaustive publication review.", "Effects on PEM, severe Long COVID and long-term functioning cannot be inferred from the study design.", "Sleepiness, fatigue and post-exertional symptom worsening are different problems; these findings cannot be assumed to apply to all three." ], "access": { "text": "This completed study lists US sites only. Canadian Long COVID authorization, supply and coverage have not been verified; a research listing is not a prescribing recommendation.", "source_ids": [ "modafinil-solriamfetol-registry" ] }, "next_review": "Check posted comparative outcomes, adverse events and any full publication before drawing an efficacy conclusion.", "source_checked": "2026-10-16" }, { "id": "melatonin-light", "name": "Melatonin + light therapy", "aliases": [ "RECOVER-SLEEP", "insomnia", "sleep-wake rhythm" ], "category": "Symptom management", "scope": "Sleep symptoms after COVID", "evidence_label": "Completed trial; no posted registry results", "summary": "RECOVER-SLEEP tested melatonin and tailored light for sleep problems after COVID. The completed trial has no posted registry results. This does not establish a Long COVID treatment benefit.", "summary_sources": [ "melatonin-light-registry" ], "trials": [ "NCT06404112" ], "findings": [ { "outcome": "Study design", "interpretation": "The trial compared active or placebo melatonin and active or control light, alongside a tailored sleep schedule. It studied the treatment components within one trial.", "source_ids": [ "melatonin-light-registry" ] }, { "outcome": "Results and harms", "interpretation": "No results are posted in this registry record as of 16 October 2026. Completion and enrolment counts are not evidence of benefit or safety.", "source_ids": [ "melatonin-light-registry" ] } ], "limitations": [ "This is a scoped registry summary, not an exhaustive publication review.", "Effects on PEM, severe Long COVID and long-term functioning cannot be inferred from the study design.", "Sleepiness, fatigue and post-exertional symptom worsening are different problems; these findings cannot be assumed to apply to all three." ], "access": { "text": "This completed study lists US sites only. Canadian Long COVID authorization, supply and coverage have not been verified; a research listing is not a prescribing recommendation.", "source_ids": [ "melatonin-light-registry" ] }, "next_review": "Check posted comparative outcomes, adverse events and any full publication before drawing an efficacy conclusion.", "source_checked": "2026-10-16" }, { "id": "pacing", "name": "Pacing and energy management", "aliases": [ "PEM", "PESE", "post-exertional malaise", "activity management", "crashes" ], "category": "Symptom management", "scope": "Supportive care for post-exertional symptoms", "evidence_label": "Symptom-management guidance; not a cure", "summary": "Pacing adapts activity and rest to a person’s limits to reduce post-exertional symptom flare-ups. It is supportive care, not evidence that Long COVID is cured.", "summary_sources": [ "cdc-long-covid-care", "cdc-pem-care" ], "trials": [], "findings": [ { "outcome": "Clinical guidance", "interpretation": "CDC Long COVID guidance links to activity-management approaches for PEM. Its ME/CFS resource describes balancing rest and activity within individual limits.", "source_ids": [ "cdc-long-covid-care", "cdc-pem-care" ] } ], "limitations": [ "Guidance does not provide a randomized Long COVID effect estimate.", "Individual limits differ and can change. Physical and mental activity can both trigger delayed symptoms.", "Pacing should not be turned into fixed activity increases or instructions to push through symptoms." ], "access": { "text": "Discuss an individual plan and support needs with a clinician familiar with PEM. This entry does not prescribe an activity target or a graded exercise programme.", "source_ids": [ "cdc-pem-care" ] }, "next_review": "Review Long COVID-specific comparative evidence and harms separately from clinical guidance.", "source_checked": "2026-10-16" } ], "trials": [ { "id": "NCT06161688", "intervention_id": "ensitrelvir", "name": "PREVAIL-LC", "role": "intervention_trial", "scope": "established_long_covid", "status": "ACTIVE_NOT_RECRUITING", "status_verified_by_registry": "2026-03", "registry_updated": "2026-04-02", "source_checked": "2026-10-13", "results_kind": "efficacy_and_safety_registry_results", "design": "Randomized placebo-controlled phase 2", "actual_enrolment": 40, "regimen_duration": "Five days", "primary_timepoint": "Day 10", "countries": [ "United States" ], "canadian_sites": false, "canadian_eligibility": "not_established; no current recruitment", "participation_burden": "Protocol includes walking, active-stand and cognitive assessments. A PEM questionnaire is included; its presence does not establish that exertional testing is safe for severe or housebound patients.", "source_ids": [ "prevail-registry", "prevail-ucsf", "prevail-protocol-sap" ], "analysis_plan_finalized": "2025-02-21", "primary_completion_actual": "2024-12-20" }, { "id": "NCT06305806", "intervention_id": "ivabradine", "name": "RECOVER-AUTONOMIC ivabradine", "role": "intervention_appendix", "parent_registry_id": "NCT06305780", "scope": "long_covid_pots", "status": "COMPLETED", "status_verified_by_registry": "2026-02", "registry_updated": "2026-02-20", "source_checked": "2026-10-13", "results_kind": "conference_reported_numerical_efficacy; appendix_has_no_results", "design": "Randomized placebo-controlled factorial trial with coordinated/usual care", "actual_enrolment": 181, "regimen_duration": "Three months", "follow_up": "Additional three months", "countries": [ "United States" ], "canadian_sites": false, "canadian_eligibility": "not_established; trial completed", "participation_burden": "Standing assessments and symptom/function measures; do not advertise this completed trial as recruiting.", "source_ids": [ "recover-appendix", "recover-announcement", "recover-seminar", "recover-acc-slides" ] }, { "id": "NCT06305780", "intervention_id": null, "name": "RECOVER-AUTONOMIC platform", "role": "platform_parent_not_independent_ivabradine_trial", "scope": "related_parent_record", "status": "COMPLETED", "registry_updated": "2026-08-03", "source_checked": "2026-10-13", "results_kind": "enrolment_only_for_this_pilot", "actual_enrolment": 381, "enrolment_by_appendix": { "ivig": 200, "ivabradine": 181 }, "safety_interpretation": "Event rows have zero denominators; not usable as zero-event safety estimates.", "source_ids": [ "recover-platform" ] }, { "id": "NCT05481177", "intervention_id": "ivabradine", "name": "COVIVA", "role": "intervention_trial", "scope": "long_covid_pots", "status": "UNKNOWN", "last_known_status": "RECRUITING", "status_verified_by_registry": "2023-11", "registry_updated": "2023-11-29", "source_checked": "2026-10-13", "recruitment_verification": "Registry remains UNKNOWN. Institutional project listing identifies COVIVA but does not confirm current recruitment.", "results_kind": "protocol_only; no_registry_results", "design": "Randomized nested trial within a cohort", "planned_enrolment": 250, "planned_enrolment_note": "Registry total; do not assume all 250 receive the randomized drug comparison.", "countries": [ "United States" ], "canadian_sites": false, "canadian_eligibility": "unknown", "participation_burden": "Requires confirmation from current investigator information.", "source_ids": [ "coviva-registry", "coviva-protocol", "coviva-institution" ] }, { "id": "NCT05715528", "intervention_id": "obeldesivir", "name": "OAKTREE", "role": "contextual_trial", "scope": "acute_covid_not_established_long_covid", "status": "COMPLETED", "registry_updated": "2024-12-24", "source_checked": "2026-10-13", "results_kind": "published_efficacy_and_registry_results", "design": "Phase 3 randomized placebo-controlled acute-COVID trial", "randomized_and_dosed": 1955, "primary_analysis_denominators": [ 879, 882 ], "countries": [ "Japan", "United States" ], "canadian_eligibility": "not_a_recruiting_long_covid_trial", "source_ids": [ "oaktree-paper", "oaktree-registry" ] }, { "id": "NCT05603143", "intervention_id": "obeldesivir", "name": "BIRCH", "role": "contextual_trial", "scope": "acute_covid_not_established_long_covid", "status": "TERMINATED", "why_stopped": "Low primary-endpoint event count; registry explanation.", "registry_updated": "2024-12-20", "source_checked": "2026-10-13", "results_kind": "published_efficacy_and_registry_results", "design": "Phase 3 randomized placebo-controlled acute-COVID trial", "randomized_and_dosed": 465, "primary_analysis_denominators": [ 211, 207 ], "canadian_eligibility": "not_a_recruiting_long_covid_trial", "source_ids": [ "birch-paper", "birch-registry" ] }, { "id": "NCT05576662", "intervention_id": "paxlovid", "intervention_ids": [ "paxlovid" ], "name": "STOP-PASC", "role": "intervention_trial", "scope": "established_long_covid", "status": "COMPLETED", "status_verified_by_registry": "2025-08", "registry_updated": "2025-09-04", "source_checked": "2026-10-13", "results_kind": "published_efficacy_and_registry_results", "design": "Randomized masked placebo-controlled phase 2", "actual_enrolment": 168, "countries": [ "United States" ], "canadian_sites": false, "canadian_recruiting_sites": [], "canadian_eligibility": "Trial completed; not recruiting.", "participation_burden": "15 days; primary assessment at 10 weeks. Five clinic visits over 15 weeks.", "source_ids": [ "nct05576662" ], "published_randomized": 155, "enrolment_note": "Registry enrolment 168 corresponds to consent and screening in the publication; 155 were randomized." }, { "id": "NCT05668091", "intervention_id": "paxlovid", "intervention_ids": [ "paxlovid" ], "name": "PAX LC", "role": "intervention_trial", "scope": "established_long_covid", "status": "COMPLETED", "status_verified_by_registry": "2024-11", "registry_updated": "2024-12-02", "source_checked": "2026-10-13", "results_kind": "published_efficacy; no_registry_results", "design": "Randomized masked placebo-controlled phase 2", "actual_enrolment": 100, "countries": [ "United States" ], "canadian_sites": false, "canadian_recruiting_sites": [], "canadian_eligibility": "Trial completed; not recruiting.", "participation_burden": "15 days; primary assessment at day 28. Decentralized US trial with no required site visits.", "source_ids": [ "nct05668091" ] }, { "id": "NCT05965726", "intervention_id": "paxlovid", "intervention_ids": [ "paxlovid" ], "name": "RECOVER-VITAL", "role": "intervention_appendix", "scope": "established_long_covid", "status": "COMPLETED", "status_verified_by_registry": "2026-03", "registry_updated": "2026-03-27", "source_checked": "2026-10-13", "results_kind": "published_efficacy_and_registry_results", "design": "Randomized masked placebo-controlled phase 2", "actual_enrolment": 964, "countries": [ "United States" ], "canadian_sites": false, "canadian_recruiting_sites": [], "canadian_eligibility": "Trial completed; not recruiting.", "participation_burden": "15 or 25 days; primary assessment at day 90. Symptom and performance assessments.", "source_ids": [ "nct05965726", "vital-full" ], "parent_registry_id": "NCT05595369", "multiple_phenotype_participants": 31, "phenotype_counts_are_disjoint": false }, { "id": "NCT05430152", "intervention_id": "ldn", "intervention_ids": [ "ldn" ], "name": "BC low-dose naltrexone trial", "role": "intervention_trial", "scope": "established_long_covid", "status": "COMPLETED", "status_verified_by_registry": "2026-03", "registry_updated": "2026-03-20", "source_checked": "2026-10-13", "results_kind": "no_registry_results; protocol_published", "design": "Randomized masked placebo-controlled phase 2", "actual_enrolment": 160, "countries": [ "Canada" ], "canadian_sites": true, "canadian_recruiting_sites": [], "canadian_eligibility": "Trial completed; not recruiting.", "participation_burden": "16-week trial with fatigue questionnaires and blood measures. Completed.", "source_ids": [ "nct05430152" ] }, { "id": "NCT06366724", "intervention_id": null, "intervention_ids": [ "ldn", "pyridostigmine" ], "name": "LIFT", "role": "shared_factorial_trial", "scope": "mecfs_with_orthostatic_intolerance_including_eligible_long_covid", "status": "RECRUITING", "status_verified_by_registry": "2025-10", "registry_updated": "2025-10-22", "source_checked": "2026-10-13", "results_kind": "published_protocol; no_registry_results", "design": "Randomized masked placebo-controlled phase 2", "planned_enrolment": 160, "countries": [ "United States" ], "canadian_sites": false, "canadian_recruiting_sites": [], "canadian_eligibility": "No Canadian site listed; cross-border eligibility not established.", "participation_burden": "Approximately three months, three in-person Boston visits and four virtual visits; two submaximal cardiopulmonary exercise tests, blood and urine collection. Exertional testing can be burdensome with PEM; discuss accommodations and suitability with the study team.", "source_ids": [ "nct06366724", "lift-protocol" ], "planned_enrolment_note": "160 total across four arms shared between LDN and pyridostigmine; not 160 per drug.", "recruitment_verification": "Registry says recruiting but was last updated October 2025; estimated September 2026 primary completion has passed. Current availability requires confirmation.", "protocol_note": "The August 2026 protocol describes 13 weeks of treatment after screening, four factorial arms and function/physiology outcomes. It supplies no efficacy results or current enrolment confirmation." }, { "id": "NCT06305793", "intervention_id": "ivig", "intervention_ids": [ "ivig" ], "name": "RECOVER-AUTONOMIC IVIG", "role": "intervention_appendix", "scope": "long_covid_pots", "status": "COMPLETED", "status_verified_by_registry": "2026-07", "registry_updated": "2026-07-31", "source_checked": "2026-10-13", "results_kind": "no_registry_results", "design": "Randomized masked placebo-controlled phase 2", "actual_enrolment": 200, "countries": [ "United States" ], "canadian_sites": false, "canadian_recruiting_sites": [], "canadian_eligibility": "Trial completed; not recruiting.", "participation_burden": "Repeated IV infusions over nine months, followed by three months of follow-up; orthostatic symptoms assessed at nine months.", "source_ids": [ "nct06305793" ], "parent_registry_id": "NCT06305780" }, { "id": "NCT05350774", "intervention_id": "ivig", "intervention_ids": [ "ivig" ], "name": "NIH neurological Long COVID IVIG study", "role": "intervention_trial", "scope": "established_long_covid", "status": "ENROLLING_BY_INVITATION", "status_verified_by_registry": "2026-08-24", "registry_updated": "2026-10-13", "source_checked": "2026-10-13", "results_kind": "no_registry_results", "design": "Randomized masked placebo-controlled phase 2", "planned_enrolment": 45, "countries": [ "United States" ], "canadian_sites": false, "canadian_recruiting_sites": [], "canadian_eligibility": "No Canadian site listed; cross-border eligibility not established.", "participation_burden": "Invitation-only NIH study requiring prior protocol participation. Procedures include infusion courses, lumbar puncture, tilt testing and neurological assessments; up to four months.", "source_ids": [ "nct05350774" ] }, { "id": "NCT06928272", "intervention_id": "upadacitinib", "intervention_ids": [ "upadacitinib", "pirfenidone" ], "name": "LC-REVITALIZE", "role": "multi_intervention_platform", "scope": "established_long_covid", "status": "RECRUITING", "status_verified_by_registry": "2026-10", "registry_updated": "2026-10-06", "source_checked": "2026-10-14", "results_kind": "no_registry_results", "design": "Randomized masked placebo-controlled phase 3", "planned_enrolment": 348, "countries": [ "United States", "Brazil", "Canada", "Italy", "South Africa", "Uganda", "Zambia" ], "canadian_sites": true, "canadian_recruiting_sites": [ { "facility": "Institut de Recherches Cliniques de Montréal (IRCM)", "city": "Montreal", "province": "Quebec", "status": "RECRUITING" }, { "facility": "Centre de Recherche du CHUS (CRCHUS)", "city": "Sherbrooke", "province": "Quebec", "status": "RECRUITING" } ], "canadian_eligibility": "Registry lists Canadian sites as recruiting; site and specific drug-arm availability require confirmation.", "participation_burden": "Three months of study medication with follow-up to six months. Confirm eligibility, visits, monitoring and the locally available drug arm with the study team.", "source_ids": [ "nct06928272", "revitalize-quebec" ], "planned_enrolment_note": "348 across upadacitinib, pirfenidone and matched placebo groups in the initial platform phase; not 348 on upadacitinib.", "recruitment_verification": "ClinicalTrials.gov and a derived Quebec listing identify Montreal and Sherbrooke sites; no direct study-team confirmation of current drug-arm availability.", "directory_url": "/research/canada/#NCT06928272" }, { "id": "ISRCTN10665760", "intervention_ids": [ "famotidine-loratadine", "colchicine", "rivaroxaban" ], "name": "STIMULATE-ICP drug trial", "role": "shared_multi_arm_trial", "scope": "established_long_covid", "status": "COMPLETED", "status_basis": "Published full report; not a fresh registry-status check", "source_checked": "2026-10-14", "results_kind": "published_randomized_results", "design": "Open-label randomized four-group trial; all groups received specialist usual care", "enrolment": 778, "allocation": { "colchicine": 192, "famotidine-loratadine": 193, "rivaroxaban": 197, "no_study_drug": 196 }, "countries": [ "United Kingdom" ], "canadian_sites": false, "canadian_recruiting_sites": [], "canadian_eligibility": "Completed UK study; not a Canadian recruitment opportunity.", "participation_burden": "Study drugs for 12 weeks; fatigue questionnaires at baseline, 12 and 24 weeks. Published trial regimens are research descriptions, not prescribing instructions.", "source_ids": [ "stimulate-drug-paper" ], "url": "https://www.isrctn.com/ISRCTN10665760" }, { "id": "CTRI/2021/11/038234", "intervention_id": "colchicine", "intervention_ids": [ "colchicine" ], "name": "Colchicine trial — India", "role": "individual_trial", "scope": "post_covid_functional_limitation_or_inflammation", "status": "COMPLETED", "status_basis": "Published completed trial report", "source_checked": "2026-10-14", "results_kind": "published_randomized_results", "design": "Double-blind randomized placebo-controlled trial", "enrolment": 350, "analysis_n": 319, "safety_n": 346, "countries": [ "India" ], "canadian_sites": false, "canadian_recruiting_sites": [], "canadian_eligibility": "Completed study; not a Canadian recruitment opportunity.", "participation_burden": "26 weeks of study medication; primary walking-distance outcome at 52 weeks. Walking assessments may not represent what severely affected or housebound patients can tolerate.", "source_ids": [ "colchicine-india-paper" ], "url": "https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2840468" }, { "id": "NCT04647656", "name": "HBOT 40-session trial — Israel", "enrolment": 79, "analysis_n": 73, "countries": [ "Israel" ], "source_ids": [ "hbot-israel-paper" ], "participation_burden": "40 chamber sessions; outcomes assessed 1–3 weeks after treatment. The Results section reports 79 randomized and 73 analyzed; the abstract calls 73 randomized.", "intervention_id": "hbot", "intervention_ids": [ "hbot" ], "role": "individual_trial", "scope": "established_long_covid", "status": "COMPLETED", "status_basis": "Published completed trial report", "source_checked": "2026-10-14", "results_kind": "published_randomized_results", "design": "Randomized sham/placebo-controlled trial", "canadian_sites": false, "canadian_recruiting_sites": [], "canadian_eligibility": "Completed study; not a current recruitment opportunity." }, { "id": "NCT04842448", "name": "HOT-LoCO — Sweden", "enrolment": 80, "analysis_n": 79, "countries": [ "Sweden" ], "source_ids": [ "hbot-hotloco-paper" ], "participation_burden": "10 chamber sessions over six weeks; primary physical-health outcomes at 13 weeks.", "intervention_id": "hbot", "intervention_ids": [ "hbot" ], "role": "individual_trial", "scope": "established_long_covid", "status": "COMPLETED", "status_basis": "Published completed trial report", "source_checked": "2026-10-14", "results_kind": "published_randomized_results", "design": "Randomized sham/placebo-controlled trial", "canadian_sites": false, "canadian_recruiting_sites": [], "canadian_eligibility": "Completed study; not a current recruitment opportunity." }, { "id": "HBOT-BELGIUM-2025", "id_type": "local_report_identifier_not_registry_id", "name": "Four-group oxygen trial — Belgium", "enrolment": 101, "countries": [ "Belgium" ], "source_ids": [ "hbot-belgium-paper" ], "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12267068/", "participation_burden": "10 chamber sessions with four oxygen/pressure conditions; repeated cognitive and walking tests. Travel and attendance burden were reported.", "intervention_id": "hbot", "intervention_ids": [ "hbot" ], "role": "individual_trial", "scope": "established_long_covid", "status": "COMPLETED", "status_basis": "Published completed trial report", "source_checked": "2026-10-14", "results_kind": "published_randomized_results", "design": "Randomized sham/placebo-controlled trial", "canadian_sites": false, "canadian_recruiting_sites": [], "canadian_eligibility": "Completed study; not a current recruitment opportunity." }, { "id": "NCT06452095", "intervention_id": "hbot", "intervention_ids": [ "hbot" ], "name": "RECLAIM — hyperbaric oxygen", "role": "individual_trial", "scope": "established_long_covid", "status": "RECRUITING", "source_checked": "2026-10-13", "registry_updated": "2026-02-23", "results_kind": "outcomes_not_assessed_in_this_update", "countries": [ "Canada" ], "canadian_sites": true, "canadian_recruiting_sites": [ { "facility": "University Health Network", "city": "Toronto", "province": "Ontario", "status": "RECRUITING" } ], "canadian_eligibility": "Canadian registry site listed as recruiting; confirm current openings and eligibility with the team.", "participation_burden": "Tests hyperbaric oxygen for Long COVID cognitive symptoms. Ask the team about chamber visits, travel and the assessment schedule. Ask the study team about visits, time, travel, compensation, accessibility and any exertion or testing requirements.", "source_ids": [ "reclaim-hbot-registry" ], "directory_url": "/research/canada/#NCT06452095" }, { "id": "NCT06082518", "intervention_id": "hbot", "intervention_ids": [ "hbot" ], "name": "Hyperbaric oxygen for post-COVID symptoms", "role": "individual_trial", "scope": "established_long_covid", "status": "ACTIVE_NOT_RECRUITING", "source_checked": "2026-10-13", "registry_updated": "2026-09-02", "results_kind": "outcomes_not_assessed_in_this_update", "countries": [ "Canada" ], "canadian_sites": true, "canadian_recruiting_sites": [], "canadian_eligibility": "Ongoing follow-up; registry lists no new recruitment.", "participation_burden": "Studies hyperbaric oxygen treatment for post-COVID symptoms. Follow-up is ongoing; the registry says new participants are not being accepted. Ask the study team about visits, time, travel, compensation, accessibility and any exertion or testing requirements.", "source_ids": [ "sunnybrook-hbot-registry" ], "directory_url": "/research/canada/#NCT06082518" }, { "id": "NCT06721949", "intervention_id": "taurine", "intervention_ids": [ "taurine" ], "name": "RECLAIM — taurine", "role": "individual_trial", "scope": "established_long_covid", "status": "RECRUITING", "registry_updated": "2026-09-18", "source_checked": "2026-10-14", "results_kind": "no_registry_results", "design": "Randomized controlled trial", "planned_enrolment": 300, "countries": [ "Canada" ], "canadian_sites": true, "canadian_recruiting_sites": [ { "facility": "University of Alberta Hospital, Kaye Edmonton Clinic", "city": "Edmonton", "province": "Alberta", "status": "RECRUITING" }, { "facility": "BC Women's Hospital", "city": "Vancouver", "province": "British Columbia", "status": "RECRUITING" }, { "facility": "University Health Network", "city": "Toronto", "province": "Ontario", "status": "RECRUITING" }, { "facility": "Institut de recherches cliniques de Montréal", "city": "Montreal", "province": "Quebec", "status": "RECRUITING" }, { "facility": "Centre intégré universitaire de santé et de services sociaux de l'Estrie - Centre hospitalier universitaire de Sherbrooke", "city": "Sherbrooke", "province": "Quebec", "status": "RECRUITING" } ], "canadian_eligibility": "Canadian sites listed as recruiting; eligibility and current local openings require team confirmation.", "participation_burden": "12 weeks of taurine or placebo followed by 12 weeks of follow-up; fatigue and cognitive testing plus other assessments. Confirm visit and exertion requirements with the team.", "source_ids": [ "nct06721949" ], "directory_url": "/research/canada/#NCT06721949" }, { "id": "NCT06928506", "intervention_id": "hioxsr", "intervention_ids": [ "hioxsr" ], "name": "RECLAIM-HiOxSR", "role": "individual_trial", "scope": "established_long_covid", "status": "RECRUITING", "registry_updated": "2025-09-15", "source_checked": "2026-10-14", "results_kind": "no_registry_results", "design": "Randomized active-control device study; participants know allocation but are masked to the hypothesis", "planned_enrolment": 120, "countries": [ "Canada" ], "canadian_sites": true, "canadian_recruiting_sites": [ { "facility": "University Health Network", "city": "Toronto", "province": "Ontario", "status": "RECRUITING" } ], "canadian_eligibility": "Canadian sites listed as recruiting; eligibility and current local openings require team confirmation.", "participation_burden": "Three device-use groups over two or four weeks with cognitive follow-up to two months. Device training, monitoring and site visits require confirmation. This is not HBOT or a home-use instruction.", "source_ids": [ "nct06928506" ], "directory_url": "/research/canada/#NCT06928506", "recruitment_note": "Older registry marks Edmonton and Sherbrooke not yet recruiting; RECLAIM website lists enrollment open. Confirm the site with the study team." }, { "id": "NCT07374562", "intervention_id": "sgb", "intervention_ids": [ "sgb" ], "name": "STAR-CO", "role": "individual_trial", "scope": "established_long_covid", "status": "RECRUITING", "registry_updated": "2026-02-09", "source_checked": "2026-10-14", "results_kind": "no_registry_results", "design": "Randomized controlled trial", "planned_enrolment": 40, "countries": [ "Canada" ], "canadian_sites": true, "canadian_recruiting_sites": [ { "facility": "Centre hospitalier affilié universitaire régional", "city": "Trois-Rivières", "province": "Quebec", "status": "RECRUITING" } ], "canadian_eligibility": "Canadian sites listed as recruiting; eligibility and current local openings require team confirmation.", "participation_burden": "Injection procedure with primary symptom/function assessments at four weeks and follow-up through 26 weeks. Ask about procedural risks, monitoring and travel.", "source_ids": [ "nct07374562" ], "directory_url": "/research/canada/#NCT07374562" }, { "id": "NCT07468604", "intervention_id": "sgb", "intervention_ids": [ "sgb" ], "name": "CeASE", "role": "individual_trial", "scope": "established_long_covid", "status": "RECRUITING", "registry_updated": "2026-10-09", "source_checked": "2026-10-14", "results_kind": "no_registry_results", "design": "Randomized controlled trial", "planned_enrolment": 78, "countries": [ "Canada" ], "canadian_sites": true, "canadian_recruiting_sites": [ { "facility": "Toronto Western Hospital", "city": "Toronto", "province": "Ontario", "status": "RECRUITING" } ], "canadian_eligibility": "Canadian sites listed as recruiting; eligibility and current local openings require team confirmation.", "participation_burden": "Two injection procedures over six weeks; symptom and autonomic assessments afterward. Toronto Western is listed recruiting; Women's College is not yet recruiting.", "source_ids": [ "nct07468604" ], "directory_url": "/research/canada/#NCT07468604" }, { "id": "NCT07682402", "intervention_id": "taurine", "intervention_ids": [ "taurine" ], "name": "TaurineLCPeds", "role": "individual_trial", "scope": "established_long_covid", "status": "NOT_YET_RECRUITING", "registry_updated": "2026-08-13", "source_checked": "2026-10-14", "results_kind": "no_registry_results", "design": "Open-label single-group study", "planned_enrolment": 30, "countries": [ "Canada" ], "canadian_sites": false, "canadian_recruiting_sites": [], "canadian_eligibility": "Canadian-led; not yet recruiting. Study sites and actual start require confirmation.", "participation_burden": "Three months of supplementation with blood sampling and symptom/cognitive assessments. Ask about study locations, visit schedule, accessibility, travel and current opening date. The primary outcome is change in blood taurine, not proof of symptom benefit.", "source_ids": [ "nct07682402" ], "directory_url": "/research/canada/#NCT07682402" }, { "id": "NCT04607928", "intervention_id": "pirfenidone", "intervention_ids": [ "pirfenidone" ], "name": "FIBRO-COVID", "role": "individual_trial", "scope": "post_severe_covid_pulmonary_fibrosis_not_general_long_covid", "status": "COMPLETED", "status_basis": "Published completed-trial report; not a new registry-status check", "source_checked": "2026-10-14", "results_kind": "published_randomized_results", "design": "Double-blind randomized placebo-controlled trial", "enrolment": 113, "analysis_n": 103, "countries": [ "Spain" ], "canadian_sites": false, "canadian_recruiting_sites": [], "canadian_eligibility": "Completed Spanish study; not a Canadian recruitment opportunity.", "participation_burden": "24 weeks of treatment with lung function, CT imaging and other assessments; enrolled after severe COVID-19 pneumonia.", "source_ids": [ "pirfenidone-fibro", "pirfenidone-correction" ] }, { "id": "NCT06253806", "intervention_id": "sgb", "intervention_ids": [ "sgb" ], "name": "Stellate ganglion block for post-COVID parosmia", "role": "individual_trial", "scope": "post_covid_parosmia", "status": "COMPLETED", "status_basis": "Published completed-trial report; not a new registry-status check", "source_checked": "2026-10-14", "results_kind": "published_randomized_results", "design": "Double-blind randomized saline-controlled trial", "enrolled_n": 57, "analysis_n": 48, "three_month_analysis_n": 46, "countries": [ "United States" ], "canadian_sites": false, "canadian_recruiting_sites": [], "canadian_eligibility": "Completed US study; not a Canadian recruitment opportunity.", "participation_burden": "A single ultrasound-guided injection, with symptom follow-up at one and three months. Canadian protocols differ.", "source_ids": [ "sgb-parosmia" ] }, { "id": "NCT06907251", "intervention_id": "dapagliflozin", "intervention_ids": [ "dapagliflozin" ], "name": "DALCO", "role": "individual_trial", "scope": "established_long_covid", "status": "NOT_YET_RECRUITING", "registry_updated": "2026-07-01", "source_checked": "2026-10-15", "results_kind": "no_registry_results", "design": "Randomized placebo-controlled trial", "planned_enrolment": 192, "countries": [ "Canada" ], "canadian_sites": true, "canadian_recruiting_sites": [], "canadian_eligibility": "Not yet recruiting; confirm opening and eligibility with the study team.", "participation_burden": "Planned 12-month treatment with follow-up assessments; ask about visits, monitoring and optional MRI requirements.", "source_ids": [ "dalco-registry" ], "directory_url": "/research/canada/#NCT06907251" }, { "id": "NCT06404099", "intervention_id": "modafinil-solriamfetol", "intervention_ids": [ "modafinil-solriamfetol" ], "name": "RECOVER-SLEEP: Modafinil or solriamfetol", "role": "individual_trial", "scope": "established_long_covid", "status": "COMPLETED", "registry_updated": "2026-06-03", "source_checked": "2026-10-16", "results_kind": "no_registry_results", "design": "Randomized placebo-controlled trial", "actual_enrolment": 361, "countries": [ "United States" ], "canadian_sites": false, "canadian_recruiting_sites": [], "canadian_eligibility": "Completed US trial; not an open Canadian participation opportunity.", "participation_burden": "Historical trial requirements; not currently enrolling.", "source_ids": [ "modafinil-solriamfetol-registry" ] }, { "id": "NCT06404112", "intervention_id": "melatonin-light", "intervention_ids": [ "melatonin-light" ], "name": "RECOVER-SLEEP: Melatonin + light therapy", "role": "individual_trial", "scope": "established_long_covid", "status": "COMPLETED", "registry_updated": "2026-07-08", "source_checked": "2026-10-16", "results_kind": "no_registry_results", "design": "Randomized placebo-controlled trial", "actual_enrolment": 469, "countries": [ "United States" ], "canadian_sites": false, "canadian_recruiting_sites": [], "canadian_eligibility": "Completed US trial; not an open Canadian participation opportunity.", "participation_burden": "Historical trial requirements; not currently enrolling.", "source_ids": [ "melatonin-light-registry" ] } ], "search_log": [ { "date": "2026-10-13", "database": "ClinicalTrials.gov API v2", "query": { "intervention": "ensitrelvir", "condition": "Long COVID" }, "url": "https://clinicaltrials.gov/api/v2/studies?query.intr=ensitrelvir&query.cond=Long%20COVID&pageSize=100&countTotal=true", "matches": 1, "limitation": "Scoped query; terminology and registration coverage can omit relevant studies." }, { "date": "2026-10-13", "database": "ClinicalTrials.gov API v2", "query": { "intervention": "obeldesivir", "condition": "Long COVID" }, "url": "https://clinicaltrials.gov/api/v2/studies?query.intr=obeldesivir&query.cond=Long%20COVID&pageSize=100&countTotal=true", "matches": 0, "limitation": "Scoped query; terminology and registration coverage can omit relevant studies." }, { "date": "2026-10-13", "database": "ClinicalTrials.gov API v2", "query": { "intervention": "ivabradine", "condition": "Long COVID" }, "url": "https://clinicaltrials.gov/api/v2/studies?query.intr=ivabradine&query.cond=Long%20COVID&pageSize=100&countTotal=true", "matches": 3, "limitation": "Scoped query; terminology and registration coverage can omit relevant studies." }, { "date": "2026-10-13", "database": "ClinicalTrials.gov API v2", "query": { "intervention": "obeldesivir", "condition": "unrestricted" }, "url": "https://clinicaltrials.gov/api/v2/studies?query.intr=obeldesivir&pageSize=100&countTotal=true", "matches": 6, "matched_ids": [ "NCT06682234", "NCT06585150", "NCT05996744", "NCT05715528", "NCT06784973", "NCT05603143" ], "established_long_covid_trials_identified": 0, "limitation": "Single-registry, named-intervention query; aliases and unregistered studies can be missed." }, { "date": "2026-10-13", "database": "Web search of primary sources", "queries": [ "\"PREVAIL-LC\" results ensitrelvir Henrich 2026 PROMIS", "\"RECOVER-AUTONOMIC\" \"Taub\" \"results\" site:pubmed.ncbi.nlm.nih.gov", "site:health-products.canada.ca \"ensitrelvir\"", "site:health-products.canada.ca \"obeldesivir\"", "site:health-products.canada.ca \"Xocova\"" ], "result": "Located PREVAIL SAP and RECOVER investigator slides; no full PREVAIL results publication or full RECOVER efficacy journal report identified. No antiviral Canadian marketing record identified by web search.", "limitation": "Web indexing is incomplete. This is not a definitive Drug Product Database search and does not prove absence of approval or publication." }, { "date": "2026-10-13", "database": "ClinicalTrials.gov API v2", "query": { "intervention": "nirmatrelvir", "condition": "Long COVID" }, "url": "https://clinicaltrials.gov/api/v2/studies?query.intr=nirmatrelvir&query.cond=Long%20COVID&pageSize=100&countTotal=true", "matches": 11, "limitation": "Curated selection. Raw matches include unrelated, combination, prevention and parent records; not a count of eligible treatment trials." }, { "date": "2026-10-13", "database": "ClinicalTrials.gov API v2", "query": { "intervention": "naltrexone", "condition": "Long COVID" }, "url": "https://clinicaltrials.gov/api/v2/studies?query.intr=naltrexone&query.cond=Long%20COVID&pageSize=100&countTotal=true", "matches": 3, "limitation": "Curated selection. Raw matches include unrelated, combination, prevention and parent records; not a count of eligible treatment trials." }, { "date": "2026-10-13", "database": "ClinicalTrials.gov API v2", "query": { "intervention": "immunoglobulin", "condition": "Long COVID" }, "url": "https://clinicaltrials.gov/api/v2/studies?query.intr=immunoglobulin&query.cond=Long%20COVID&pageSize=100&countTotal=true", "matches": 27, "limitation": "Curated selection. Raw matches include unrelated, combination, prevention and parent records; not a count of eligible treatment trials." }, { "date": "2026-10-13", "database": "ClinicalTrials.gov API v2", "query": { "intervention": "pyridostigmine", "condition": "Long COVID" }, "url": "https://clinicaltrials.gov/api/v2/studies?query.intr=pyridostigmine&query.cond=Long%20COVID&pageSize=100&countTotal=true", "matches": 1, "limitation": "Curated selection. Raw matches include unrelated, combination, prevention and parent records; not a count of eligible treatment trials." }, { "date": "2026-10-13", "database": "ClinicalTrials.gov API v2", "query": { "intervention": "upadacitinib", "condition": "Long COVID" }, "url": "https://clinicaltrials.gov/api/v2/studies?query.intr=upadacitinib&query.cond=Long%20COVID&pageSize=100&countTotal=true", "matches": 1, "limitation": "Curated selection. Raw matches include unrelated, combination, prevention and parent records; not a count of eligible treatment trials." }, { "date": "2026-10-13", "database": "Primary-source web search and live ClinicalTrials.gov API", "queries": [ "\"NCT05430152\" results naltrexone 2026", "\"NCT06305793\" results IVIG 2026", "site.omf.ngo LIFT trial recruiting 2026", "\"LC-REVITALIZE\" \"IRCM\"", "\"LC-REVITALIZE\" \"Sherbrooke\"", "\"PREVAIL-LC\" ensitrelvir results publication 2026" ], "result": "BC LDN and RECOVER IVIG records remain completed without posted results; no new primary outcome report identified in this scoped search. Retrieved LIFT protocol and RECOVER-VITAL full report. Quebec listing is registry-derived.", "limitation": "Not a systematic literature review. No investigator has been contacted; absence of a located report is not proof that none exists." }, { "date": "2026-10-14", "database": "Targeted primary-publication review and investigator website", "queries": [ "STIMULATE-ICP drug trial full report", "colchicine Long COVID randomized trial", "hyperbaric oxygen Long COVID randomized 2026" ], "result": "Reviewed full published reports for STIMULATE-ICP, the India colchicine trial, the 2022 HBOT study, HOT-LoCO and the Belgian oxygen trial. Added three HBOT reports rather than stopping at the first two. Canadian recruitment dates are carried forward from the 13 October directory audit.", "limitation": "Targeted update, not a systematic review. Full protocol/supplement reconciliation, formal risk-of-bias assessment and Canadian regulatory/coverage review are incomplete. No investigator contact." }, { "date": "2026-10-14", "database": "ClinicalTrials.gov live API, primary publications and investigator/manufacturer-hosted research abstract", "queries": [ "taurine Long COVID trial results", "Hi-OxSR Parhizgar pilot", "pirfenidone FIBRO-COVID correction", "stellate ganglion block Long COVID randomized trial" ], "result": "Retrieved six live Canadian registry records with no posted results; checked taurine biomarker study, FIBRO-COVID and its affiliation correction, Hi-OxSR pilot abstract, parosmia RCT and retrospective SGB cohort. Added missing adolescent taurine listing.", "limitation": "Targeted review, not systematic. Hi-OxSR pilot is a manufacturer-hosted abstract. Canadian authorization, coverage and direct site availability remain unverified." }, { "date": "2026-10-14", "database": "Targeted primary-publication search and live ClinicalTrials.gov API", "queries": [ "guanfacine N-acetylcysteine Long COVID randomized trial results 2025 2026", "ClinicalTrials.gov query.intr=guanfacine + query.cond=Long COVID", "ClinicalTrials.gov query.intr=guanfacine across all conditions" ], "result": "Read the 12-patient combination case series, separate 2024 guanfacine-only case report and 2025 patient survey. The condition-specific query returned zero records. The broader query returned 97 records; all titles, conditions and intervention fields were screened. No trial specifically testing the combination for Long COVID cognition was identified. DBPOTS (NCT07757555) concerns guanfacine/cromolyn for POTS, not this combination for cognition; it is not counted as direct evidence or a Canadian Long COVID opportunity.", "limitation": "Targeted search, not systematic or exhaustive. Search terminology, other registries and unpublished studies may be missed. No formal risk-of-bias rating, complete survey subgroup extraction or Canadian regulatory/coverage review." }, { "date": "2026-10-15", "database": "ClinicalTrials.gov", "queries": [ "NCT06907251 full registry record" ], "result": "Added planned DALCO study context, not a claim of efficacy. Record remains NOT_YET_RECRUITING; no results module.", "limitation": "Single-record review; no exhaustive dapagliflozin literature or Canadian prescribing/coverage review." } ], "review_queue": [ { "id": "ens-contrast", "priority": "before_efficacy_publication", "owner": "evidence reviewer (not assigned)", "dependency": "Full primary analysis and verified unblinding chronology", "action": "Plan method verified; obtain contrast CI/p-value and assess the SAP finalization date without assuming unblinding timing.", "trigger": "Before publishing an efficacy judgment or when a full results report appears.", "status": "partially_resolved", "last_checked": "2026-10-13" }, { "id": "iva-efficacy", "priority": "before_efficacy_publication", "owner": "evidence reviewer (not assigned)", "dependency": "RECOVER full efficacy report", "action": "Conference effect/CI and interaction verified. Reconcile with full publication and comparative harms.", "trigger": "Full efficacy report or registry appendix results become available.", "status": "partially_resolved", "last_checked": "2026-10-13" }, { "id": "coviva-status", "priority": "before_recruitment_listing", "owner": "LCAC source verification", "dependency": "Current institutional recruitment page or investigator confirmation", "action": "Resolve unknown registry status; do not label recruiting from its 2023 site field.", "trigger": "Before including in a recruiting filter.", "status": "unresolved_after_institutional_check", "last_checked": "2026-10-13" }, { "id": "canadian-antiviral-access", "priority": "before_access_claim", "owner": "LCAC source verification", "dependency": "Official Canadian authorization records and manufacturer confirmation", "action": "Verify ensitrelvir/obeldesivir authorization, supply and any applicable access process.", "trigger": "Before claiming availability or a supported access route.", "status": "unresolved_after_scoped_search", "last_checked": "2026-10-13" }, { "id": "ldn-results", "priority": "next_review", "owner": "evidence reviewer (not assigned)", "dependency": "BC trial results", "action": "Locate Canadian randomized outcomes and harms.", "trigger": "Before an expanded clinical or recruitment conclusion, or when the source changes.", "status": "pending", "last_checked": "2026-10-13" }, { "id": "lift-recruitment", "priority": "next_review", "owner": "evidence reviewer (not assigned)", "dependency": "Current institutional or investigator update", "action": "August 2026 protocol found; registry still last updated October 2025. Obtain current investigator confirmation.", "trigger": "Before an expanded clinical or recruitment conclusion, or when the source changes.", "status": "protocol_found; current_recruitment_unconfirmed", "last_checked": "2026-10-13" }, { "id": "ivig-results", "priority": "next_review", "owner": "evidence reviewer (not assigned)", "dependency": "RECOVER IVIG outcome report", "action": "Review IVIG results separately from platform enrolment.", "trigger": "Before an expanded clinical or recruitment conclusion, or when the source changes.", "status": "pending", "last_checked": "2026-10-13" }, { "id": "revitalize-canada", "priority": "next_review", "owner": "evidence reviewer (not assigned)", "dependency": "Study-team confirmation", "action": "Quebec listing repeats registry-origin data. Confirm local drug-arm availability directly.", "trigger": "Before an expanded clinical or recruitment conclusion, or when the source changes.", "status": "regional_listing_checked; drug_arm_unconfirmed", "last_checked": "2026-10-13" }, { "id": "vital-full-report", "priority": "next_review", "owner": "evidence reviewer (not assigned)", "dependency": "New source information or an optional reviewer", "action": "Full-report source checks are complete. Monitor corrections and new reports; independent clinical interpretation may be requested later.", "trigger": "Before an expanded clinical or recruitment conclusion, or when the source changes.", "status": "source_check_resolved; optional_review_deferred", "last_checked": "2026-10-13" } ], "revision": "Canadian treatment connections", "changes": [ { "date": "2026-10-13", "revision": "Evidence check 2", "items": [ "Verified PREVAIL analysis method and flagged chronology for review.", "Added RECOVER numerical primary/heart-rate results and care interaction from investigator slides.", "Added Ontario limited-use coverage scope.", "Broadened obeldesivir search to all conditions; recruitment/access uncertainties remain explicit." ] }, { "date": "2026-10-13", "revision": "Eight-treatment expansion", "items": [ "Added five treatments with primary-source links.", "Linked LIFT once across two interventions and separated Canadian site listings from confirmed drug-arm access.", "Added category, search and Canadian recruiting-site filters." ] }, { "date": "2026-10-13", "revision": "Reviewer preparation", "items": [ "Verified RECOVER-VITAL arm-level safety and overlapping phenotype counts against full report.", "Added LIFT protocol and identified Quebec trial listing as registry-derived.", "Added reviewer checklist and improved printing, large-text and small-screen controls.", "Corrected expansion date to 13 October in the stated Toronto timezone; prior 14 October label used UTC." ] }, { "date": "2026-10-13", "revision": "Research information notice", "items": [ "Added a prominent not-medical-advice notice.", "Recorded that independent clinical review has not been performed and is deferred by LCAC for now.", "Made the reviewer checklist optional while retaining evidence and recruitment uncertainties." ] }, { "date": "2026-10-14", "revision": "Four published-evidence summaries added", "items": [ "Added famotidine + loratadine, colchicine, rivaroxaban and HBOT summaries with published findings, harms and limitations.", "Linked three interventions to one STIMULATE-ICP trial and preserved its shared comparator.", "Included three HBOT randomized reports and links to existing Canadian listings.", "Preserved the original eight source-check dates, beta notice and readable spacing." ] }, { "date": "2026-10-14", "revision": "Canadian treatment connections", "items": [ "Added taurine, pirfenidone, Hi-OxSR and stellate ganglion block summaries.", "Rechecked six Canadian registry records; five existing listings retain statuses and one adolescent taurine study is added as not yet recruiting.", "Linked LC-REVITALIZE to both upadacitinib and pirfenidone without duplicating the study.", "Kept observational, abstract, related-condition and randomized findings distinct." ] }, { "date": "2026-10-16", "revision": "Sleep research and pacing", "items": [ "Added two RECOVER-SLEEP summaries and pacing guidance; retained earlier source-check dates." ] } ], "updated": "2026-10-16", "disclaimer": "For information only—not medical advice, diagnosis or treatment. This tracker has not been independently clinically reviewed. Listing a treatment does not recommend it or establish that it is safe or effective. Discuss treatment decisions with a qualified healthcare professional." }