Desperate Times and Good Science: Lessons From Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP)

Siddiqui et al., Critical Care Medicine, doi:10.1097/CCM.0000000000007160, May 2026
Ivermectin for COVID-19
4th treatment shown to reduce risk in August 2020, now with p < 0.00000000001 from 106 studies, recognized in 24 countries.
Lower risk for mortality, ventilation, ICU, hospitalization, recovery, cases, and viral clearance.
No treatment is 100% effective. Protocols combine treatments.
6,600+ studies for 220+ treatments. c19early.org
Meta-analysis
Review of the REMAP-CAP trial noting that "two post hoc SAPs were developed after enrollment ended: the first, adding baseline disease states and the second, removing baseline severity adjustment. The primary outcome was changed from the 90-day mortality specified in the core protocol to OSFD at 21 days." Adjustment for baseline disease state is in the protocol.
Authors note the trend towards lower mortality for noncritical patients (32% lower), dismissing it due to the post-completion SAP removing adjustment for baseline severity, however severity was higher for ivermectin, suggesting that the actual efficacy is likely to be higher.
Authors also note that "the dose of 200 ug/kg (the lowest dose in prior trials) is an interesting choice. Ivermectin is a highly lipophilic compound; its oral bioavailability is substantially enhanced by co-administration with food; however, the protocol did not specify fed-state dosing. The drug was given as tablets dissolved in water rather than oral solution, a formulation with the potential to provide inferior absorption in patients with critical illness."
Important missing comments or errors? Let us know.
Siddiqui et al., 11 May 2026, peer-reviewed, 2 authors.
DOI record: { "DOI": "10.1097/ccm.0000000000007160", "ISSN": [ "0090-3493", "1530-0293" ], "URL": "http://dx.doi.org/10.1097/CCM.0000000000007160", "author": [ { "affiliation": [ { "name": "Divisions of Critical Care Medicine and Infectious Diseases, Wake Forest University School of Medicine, Winston-Salem, NC." } ], "family": "Siddiqui", "given": "Sabrina Z.", "sequence": "first" }, { "ORCID": "https://orcid.org/0000-0001-6234-6160", "affiliation": [ { "name": "Divisions of Critical Care Medicine and Infectious Diseases, Wake Forest University School of Medicine, Winston-Salem, NC." } ], "authenticated-orcid": false, "family": "Maves", "given": "Ryan C.", "sequence": "additional" } ], "container-title": "Critical Care Medicine", "content-domain": { "crossmark-restriction": true, "domain": [ "lww.com", "ovid.com" ] }, "created": { "date-parts": [ [ 2026, 5, 15 ] ], "date-time": "2026-05-15T12:01:32Z", "timestamp": 1778846492000 }, "deposited": { "date-parts": [ [ 2026, 5, 15 ] ], "date-time": "2026-05-15T12:01:34Z", "timestamp": 1778846494000 }, "indexed": { "date-parts": [ [ 2026, 5, 15 ] ], "date-time": "2026-05-15T12:14:04Z", "timestamp": 1778847244328, "version": "3.51.4" }, "is-referenced-by-count": 0, "issued": { "date-parts": [ [ 2026, 5, 11 ] ] }, "language": "en", "link": [ { "URL": "https://journals.lww.com/10.1097/CCM.0000000000007160", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "276", "original-title": [], "prefix": "10.1097", "published": { "date-parts": [ [ 2026, 5, 11 ] ] }, "published-online": { "date-parts": [ [ 2026, 5, 11 ] ] }, "publisher": "Ovid Technologies (Wolters Kluwer Health)", "reference": [ { "DOI": "10.1016/j.bbrc.2020.10.042", "article-title": "The broad spectrum host-directed agent ivermectin as an antiviral for SARS-CoV-2?", "author": "Jans", "doi-asserted-by": "crossref", "first-page": "163", "journal-title": "Biochem Biophys Res Commun", "key": "R1-20260515", "volume": "538", "year": "2021" }, { "DOI": "10.1097/CCM.0000000000007134", "article-title": "Ivermectin for critically and noncritically ill hospitalized patients with COVID-19: Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP).", "author": "Hashmi", "doi-asserted-by": "crossref", "journal-title": "Crit Care Med", "key": "R2-20260515", "year": "2026" }, { "DOI": "10.1001/jama.2020.17022", "article-title": "Effect of hydrocortisone on mortality and organ support in patients with severe COVID-19: The REMAP-CAP COVID-19 corticosteroid domain randomized clinical trial.", "author": "Angus", "doi-asserted-by": "crossref", "first-page": "1317", "journal-title": "JAMA", "key": "R3-20260515", "volume": "324", "year": "2020" }, { "DOI": "10.1007/s00134-021-06448-5", "article-title": "Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial.", "author": "Arabi", "doi-asserted-by": "crossref", "first-page": "867", "journal-title": "Intensive Care Med", "key": "R4-20260515", "volume": "47", "year": "2021" }, { "DOI": "10.1056/NEJMoa2103417", "article-title": "Therapeutic anticoagulation with heparin in critically ill patients with Covid-19.", "author": "Goligher", "doi-asserted-by": "crossref", "first-page": "777", "journal-title": "N Engl J Med", "key": "R5-20260515", "volume": "385", "year": "2021" }, { "DOI": "10.1001/jama.2021.18178", "article-title": "Effect of convalescent plasma on organ support-free days in critically ill patients with COVID-19: A randomized clinical trial.", "author": "Estcourt", "doi-asserted-by": "crossref", "first-page": "1690", "journal-title": "JAMA", "key": "R6-20260515", "volume": "326", "year": "2021" }, { "DOI": "10.1513/AnnalsATS.202003-192SD", "article-title": "The REMAP-CAP (Randomized Embedded Multifactorial Adaptive Platform for Community-Acquired Pneumonia) study. Rationale and design.", "author": "Angus", "doi-asserted-by": "crossref", "first-page": "879", "journal-title": "Ann Am Thorac Soc", "key": "R7-20260515", "volume": "17", "year": "2020" }, { "DOI": "10.1056/NEJMoa2100433", "article-title": "Interleukin-6 receptor antagonists in critically ill patients with Covid-19.", "author": "Gordon", "doi-asserted-by": "crossref", "first-page": "1491", "journal-title": "N Engl J Med", "key": "R8-20260515", "volume": "384", "year": "2021" }, { "DOI": "10.1016/j.antiviral.2020.104787", "article-title": "The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro.", "author": "Caly", "doi-asserted-by": "crossref", "first-page": "104787", "journal-title": "Antiviral Res", "key": "R9-20260515", "volume": "178", "year": "2020" }, { "DOI": "10.1001/jama.2022.18590", "article-title": "Effect of ivermectin vs placebo on time to sustained recovery in outpatients with mild to moderate COVID-19: A randomized clinical trial.", "author": "Naggie", "doi-asserted-by": "crossref", "first-page": "1595", "journal-title": "JAMA", "key": "R10-20260515", "volume": "328", "year": "2022" }, { "DOI": "10.1001/jama.2023.1650", "article-title": "Effect of higher-dose ivermectin for 6 days vs placebo on time to sustained recovery in outpatients with COVID-19: A randomized clinical trial.", "author": "Naggie", "doi-asserted-by": "crossref", "first-page": "888", "journal-title": "JAMA", "key": "R11-20260515", "volume": "329", "year": "2023" }, { "DOI": "10.1056/NEJMoa2115869", "article-title": "Effect of early treatment with ivermectin among patients with Covid-19.", "author": "Reis", "doi-asserted-by": "crossref", "first-page": "1721", "journal-title": "N Engl J Med", "key": "R12-20260515", "volume": "386", "year": "2022" }, { "DOI": "10.1097/MS9.0000000000002762", "article-title": "The impact of ivermectin on COVID-19 outcomes: A systematic review and meta-analysis.", "author": "Sai Yengu", "doi-asserted-by": "crossref", "first-page": "809", "journal-title": "Ann Med Surg (Lond)", "key": "R13-20260515", "volume": "87", "year": "2025" } ], "reference-count": 13, "references-count": 13, "relation": {}, "resource": { "primary": { "URL": "https://journals.lww.com/10.1097/CCM.0000000000007160" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [], "subtitle": [], "title": "Desperate Times and Good Science: Lessons From Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP)", "type": "journal-article", "update-policy": "https://doi.org/10.1097/lww.0000000000001000" }
Please send us corrections, updates, or comments. c19early involves the extraction of 200,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. IMA and WCH provide treatment protocols.
  or use drag and drop   
Submit    
Post
Share
@CovidAnalysis
FAQ
Public domain CC0 1.0