Eritoran and Apremilast in hospitalized patients with COVID-19: the REMAP-CAP Immune Modulation-2 Domain

Saito et al., CMI Communications, doi:10.1016/j.cmicom.2026.105223, NCT02735707, Sep 2026
Late treatmentRCT · 96 patients · multinational · Oct 2020 – May 2022
Eritoran for COVID-19
Trial underpowered to detect differences
RCT 104 hospitalized patients with COVID-19 showing no significant difference in organ support-free days or mortality with eritoran (TLR4 antagonist) vs. placebo.
risk of death, 26.0% higher, HR 1.26, p = 0.69, treatment 4 of 46 (8.7%), control 2 of 50 (4.0%), adjusted per study, all-cause mortality, Bayesian analysis, day 90.
risk of death, 117.4% higher, RR 2.17, p = 0.42, treatment 4 of 46 (8.7%), control 2 of 50 (4.0%), in-hospital mortality.
risk of progression, 6.8% lower, RR 0.93, p = 1.00, treatment 6 of 46 (13.0%), control 7 of 50 (14.0%), NNT 105, in-hospital death or organ support within 21 days.
organ support-free days, 1.0% lower, OR 0.99, p = 0.99, treatment 46, control 50, adjusted per study, inverted to make OR<1 favor treatment, primary outcome, RR approximated with OR.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Saito et al., 15 Sep 2026, Double Blind Randomized Controlled Trial, placebo-controlled, multiple countries, peer-reviewed, 60 authors, study period October 2020 - May 2022, trial NCT02735707 (history). Contact: hiroki.saito@marianna-u.ac.jp.
Eritoran is a synthetic glycolipid anti-inflammatory/immunomodulatory drug - a lipid A analogue that binds MD-2 and blocks activation of the Toll-like receptor 4 (TLR4) pathway, proposed for COVID-19 to reduce excessive host inflammatory signaling.
Abstract: Jouma Journal Pre-proof Eritoran and Apremilast in hospitalized patients with COVID-19: the REMAP-CAP Immune Modulation-2 Domain Hiroki Saito , Farah Al-Beidh , Derek Angus , Djillali Annane , Yaseen Arabi , Abigail Beane , Lindsay Berry , Scott Berry , Zahra Bhimani , Janis Best-Lane , Marc Bonten , Charlotte Bradbury , Frank Brunkhorst , Aidan Burrell , Meredith Buxton , Maurizio Cecconi , Allen Cheng , Matthew Cove , Lennie Derde , Lise Estcourt , Shigeki Fujitani , Herman Goossens , Anthony Gordon , Cameron Green , Rashan Haniffa , Leanne Hays , Alisa Higgins , Thomas Hills , David Huang , Nao Ichihara , Devachandran Jayakumar , Francois Lamontagne , Patrick Lawler , Elizabeth Lorenzi , John Marshall , Florian Mayr , Colin McArthur , Daniel McAuley , Shay McGuinness , Zoe McQuilten , Bryan J. McVerry , Kyohei Miyamoto , Susan Morpeth , Paul Mouncey , Srinivas Murthy , Alistair Nichol , Rachael Parke , Jane Parker , Svenja Peters , Luis Felipe Reyes , Kathryn Rowan , Marlene Santos , Christopher Seymour , Manu Shankar-Hari , Vanessa Singh , Alexis Turgeon , Anne Turner , Frank van de Veerdonk , Steve Webb , Ryan Zarychanski PII: S2950-5909(26)00053-3 DOI: https://doi.org/10.1016/j.cmicom.2026.105223 CMICOM 105223 Reference: To appear in: CMI Communications Received date: 4 June 2026 Revised date: 27 August 2026 Accepted date: 9 September 2026 Please cite this article as: Hiroki Saito , Farah Al-Beidh , Derek Angus , Djillali Annane , Yaseen Arabi , Abigail Beane , Lindsay Berry , Scott Berry , Zahra Bhimani , Janis Best-Lane , Marc Bonten , Charlotte Bradbury , Frank Brunkhorst , Aidan Burrell , Meredith Buxton , Maurizio Cecconi , Allen Cheng , Matthew Cove , Lennie Derde , Lise Estcourt , Shigeki Fujitani , Herman Goossens , Anthony Gordon , Cameron Green , Rashan Haniffa , Leanne Hays , Alisa Higgins , Thomas Hills , David Huang , Nao Ichihara , Devachandran Jayakumar , Francois Lamontagne , Patrick Lawler , Elizabeth Lorenzi , John Marshall , Florian Mayr , Colin McArthur , Daniel McAuley , Shay McGuinness , Zoe McQuilten , Bryan J. McVerry , Kyohei Miyamoto , Susan Morpeth , Paul Mouncey , Srinivas Murthy , Alistair Nichol , Rachael Parke , Jane Parker , Svenja Peters , Luis Felipe Reyes , Kathryn Rowan , Marlene Santos , Christopher Seymour , Manu Shankar-Hari , Vanessa Singh , Alexis Turgeon , Anne Turner , Frank van de Veerdonk , Steve Webb , Ryan Zarychanski , Eritoran and Apremilast in hospitalized patients with COVID-19: the REMAP-CAP Immune Modulation-2 Domain, CMI Communications (2026), doi: https://doi.org/10.1016/j.cmicom.2026.105223 This is a PDF of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability. This version will undergo additional copyediting, typesetting and review before it is published in its final form. As such, this version is no longer the Accepted Manuscript, but it is not yet the definitive Version of Record; we are providing this early version to give early visibility of the article. Please note that Elsevier's sharing policy for the Published Journal Article applies to this version, see: https://www.elsevier.com/about/ policies-and-standards/sharing#4-published-journal-article. Please also note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2026 The Author(s). Published by Elsevier..
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Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial", "doi-asserted-by": "crossref", "first-page": "1317", "issue": "13", "journal-title": "JAMA", "key": "10.1016/j.cmicom.2026.105223_bib0004", "volume": "324", "year": "2020" }, { "DOI": "10.1016/S0140-6736(21)00676-0", "article-title": "Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial", "author": "Abani", "doi-asserted-by": "crossref", "first-page": "1637", "issue": "10285", "journal-title": "The Lancet", "key": "10.1016/j.cmicom.2026.105223_bib0005", "volume": "397", "year": "2021" }, { "DOI": "10.7326/ANNALS-24-00464", "article-title": "National Institutes of Health COVID-19 Treatment Guidelines Panel: Perspectives and Lessons Learned", "author": "Gulick", "doi-asserted-by": "crossref", "first-page": "1547", "issue": "11", "journal-title": "Ann Intern 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REMAP-CAP (Randomized Embedded Multifactorial Adaptive Platform for Community-acquired Pneumonia) Study. Rationale and Design", "author": "Angus", "doi-asserted-by": "crossref", "first-page": "879", "issue": "7", "journal-title": "Annals ATS", "key": "10.1016/j.cmicom.2026.105223_bib0017", "volume": "17", "year": "2020" }, { "DOI": "10.1001/jama.2023.18592", "article-title": "Vitamin C for Patients With COVID-19: More Evidence of Lack of Efficacy in Patients With Sepsis", "author": "Jabaley", "doi-asserted-by": "crossref", "first-page": "1739", "issue": "18", "journal-title": "JAMA", "key": "10.1016/j.cmicom.2026.105223_bib0018", "volume": "330", "year": "2023" }, { "DOI": "10.1111/1346-8138.16068", "article-title": "Population pharmacokinetic and exposure–response analysis of apremilast in Japanese subjects with moderate to severe psoriasis", "author": "Okubo", "doi-asserted-by": "crossref", "first-page": "1652", "issue": "11", "journal-title": "The Journal of Dermatology", "key": "10.1016/j.cmicom.2026.105223_bib0019", "volume": "48", "year": "2021" }, { "DOI": "10.1001/jama.2025.4347", "article-title": "CONSORT 2025 Statement: Updated Guideline for Reporting Randomized Trials", "author": "Hopewell", "doi-asserted-by": "crossref", "first-page": "1998", "issue": "22", "journal-title": "JAMA", "key": "10.1016/j.cmicom.2026.105223_bib0020", "volume": "333", "year": "2025" }, { "DOI": "10.1016/j.eclinm.2023.101889", "article-title": "Report of the first seven agents in the I-SPY COVID trial: a phase 2, open label, adaptive platform randomised controlled trial", "author": "Files", "doi-asserted-by": "crossref", "journal-title": "eClinicalMedicine", "key": "10.1016/j.cmicom.2026.105223_bib0021", "volume": "58", "year": "2023" }, { "key": "10.1016/j.cmicom.2026.105223_bib0022", "unstructured": "Collaborative QLH. Quantum Leap Healthcare Collaborative Concludes Apremilast Not Likely to Reduce Time to Recovery or Mortality in Critically Ill Patients in I-SPY COVID Trial [Internet]. [cited 2025 May 20]. Available from: https://www.prnewswire.com/news-releases/quantum-leap-healthcare-collaborative-concludes-apremilast-not-likely-to-reduce-time-to-recovery-or-mortality-in-critically-ill-patients-in-i-spy-covid-trial-301246687.html" }, { "DOI": "10.1097/CCM.0b013e3181b07b78", "article-title": "Phase 2 trial of eritoran tetrasodium (E5564), a Toll-like receptor 4 antagonist, in patients with severe sepsis*", "author": "Tidswell", "doi-asserted-by": "crossref", "first-page": "72", "issue": "1", "journal-title": "Critical Care Medicine", "key": "10.1016/j.cmicom.2026.105223_bib0023", "volume": "38", "year": "2010" }, { "first-page": "152", "key": "10.1016/j.cmicom.2026.105223_bib0024", "series-title": "editor. Outcome Variables with Floor or Ceiling Effects. In: Applied Longitudinal Data Analysis for Medical Science: A Practical Guide [Internet]", "year": "2023" } ], "reference-count": 24, "references-count": 24, "relation": {}, "resource": { "primary": { "URL": "https://linkinghub.elsevier.com/retrieve/pii/S2950590926000533" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [], "subtitle": [], "title": "Eritoran and Apremilast in hospitalized patients with COVID-19: the REMAP-CAP Immune Modulation-2 Domain", "type": "journal-article", "update-policy": "https://doi.org/10.1016/elsevier_cm_policy" }
Late treatment
is less effective
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