{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T04:35:10Z","timestamp":1751603710772,"version":"3.40.5"},"reference-count":28,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T00:00:00Z","timestamp":1672790400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hydroxychloroquine (HCQ) was initially promoted as an oral therapy for early treatment of coronavirus disease 2019 (COVID\u201019). Conventional meta\u2010analyses cannot fully address the heterogeneity of different designs and outcomes of randomized controlled trials (RCTs) assessing the efficacy of HCQ in outpatients with mild COVID\u201019. We conducted a pooled analysis of individual participant data from RCTs that evaluated the effect of HCQ on hospitalization and viral load reduction in outpatients with confirmed COVID\u201019. We evaluated the overall treatment group effect by log\u2010likelihood ratio test (\u22122LL) from a generalized linear mixed model to accommodate correlated longitudinal binary data. The analysis included data from 11 RCTs. The outcome of virological effect, assessed in 1560 participants (<jats:italic>N<\/jats:italic>\u00a0=\u00a0795 HCQ, <jats:italic>N<\/jats:italic>\u00a0=\u00a0765 control), did not differ significantly between the two treatment groups (\u22122LL\u00a0=\u00a07.66; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.18) when adjusting for cohort, duration of symptoms, and comorbidities. The decline in polymerase chain reaction positive tests from day 1 to 7 was 42.0 and 41.6 percentage points in the HCQ and control groups, respectively. Among the 2037 participants evaluable for hospitalization (<jats:italic>N<\/jats:italic>\u00a0=\u00a01058 HCQ, <jats:italic>N<\/jats:italic>\u00a0=\u00a0979 control), we found no significant differences in hospitalization rate between participants receiving HCQ and controls (odds ratio 0.995; 95% confidence interval 0.614\u20131.610; \u22122LL\u00a0=\u00a00.0; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.98) when adjusting for cohort, duration of symptoms, and comorbidities. This individual participant data meta\u2010analysis of 11 HCQ trials that evaluated severe acute respiratory syndrome\u2010coronavirus 2 viral clearance and COVID\u201019 hospitalization did not show a clinical benefit of HCQ. Our meta\u2010analysis provides evidence to support the interruption in the use of HCQ in mild COVID\u201019 outpatients to reduce progression to severe disease.<\/jats:p>","DOI":"10.1111\/cts.13468","type":"journal-article","created":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T07:42:20Z","timestamp":1672904540000},"page":"524-535","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Hydroxychloroquine for treatment of non\u2010hospitalized adults with <scp>COVID<\/scp>\u201019: A meta\u2010analysis of individual participant data of randomized trials"],"prefix":"10.1111","volume":"16","author":[{"given":"Oriol","family":"Mitj\u00e0","sequence":"first","affiliation":[{"name":"Fight AIDS and Infectious Diseases Foundation  Barcelona Spain"},{"name":"Hospital Universitari Germans Trias i Pujol  Badalona Spain"},{"name":"Lihir Medical Center\u2013International SOS  Lihir Island, Papua New Guinea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilmar","family":"Reis","sequence":"additional","affiliation":[{"name":"Research Division, Cardresearch Cardiologia Assistencial e de Pesquisa Pontif\u00edcia Universidade Cat\u00f3lica de Minas Gerais  Bello Horizonte Brazil"},{"name":"Cytel Inc.  Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David R.","family":"Boulware","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Medicine, Department of Medicine University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam M.","family":"Spivak","sequence":"additional","affiliation":[{"name":"University of Utah  Salt Lake City Utah USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ammar","family":"Sarwar","sequence":"additional","affiliation":[{"name":"Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Johnston","sequence":"additional","affiliation":[{"name":"Department of Medicine and Laboratory Medicine and Pathology University of Washington  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brandon","family":"Webb","sequence":"additional","affiliation":[{"name":"Intermountain Health Care University of Utah  Salt Lake City Utah USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael D.","family":"Hill","sequence":"additional","affiliation":[{"name":"University of Calgary  Calgary Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Davey","family":"Smith","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases &amp; Global Public Health UC San Diego School of Medicine  San Diego California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Kremsner","sequence":"additional","affiliation":[{"name":"University Hospital of T\u00fcbingen  T\u00fcbingen Germany"},{"name":"Centre de Recherches M\u00e9dicales de Lambar\u00e9n\u00e9  Lambar\u00e9n\u00e9 Gabon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marla","family":"Curran","sequence":"additional","affiliation":[{"name":"Bill &amp; Melinda Gates Medical Research Institute  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Carter","sequence":"additional","affiliation":[{"name":"MMS Holdings  Canton Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jim","family":"Alexander","sequence":"additional","affiliation":[{"name":"Bill &amp; Melinda Gates Medical Research Institute  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8675-2868","authenticated-orcid":false,"given":"Marc","family":"Corbacho","sequence":"additional","affiliation":[{"name":"Fight AIDS and Infectious Diseases Foundation  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Todd C.","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Medicine, Department of Medicine University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine Huppler","family":"Hullsiek","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Medicine, Department of Medicine University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily G.","family":"McDonald","sequence":"additional","affiliation":[{"name":"Division of General Internal Medicine McGill University Health Center  Montreal Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2545-8504","authenticated-orcid":false,"given":"Rachel","family":"Hess","sequence":"additional","affiliation":[{"name":"University of Utah  Salt Lake City Utah USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Hughes","sequence":"additional","affiliation":[{"name":"Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jared M.","family":"Baeten","sequence":"additional","affiliation":[{"name":"Department of Medicine and Laboratory Medicine and Pathology University of Washington  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilan","family":"Schwartz","sequence":"additional","affiliation":[{"name":"University of Alberta  Edmonton Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luanne","family":"Metz","sequence":"additional","affiliation":[{"name":"University of Calgary  Calgary Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lawrence","family":"Richer","sequence":"additional","affiliation":[{"name":"University of Alberta  Edmonton Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kara W.","family":"Chew","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine David Geffen School of Medicine at University of California  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Daar","sequence":"additional","affiliation":[{"name":"Lundquist Institute at Harbor\u2010UCLA Medical Center  Torrance California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Wohl","sequence":"additional","affiliation":[{"name":"School of Medicine University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Dunne","sequence":"additional","affiliation":[{"name":"Bill &amp; 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