Corresponding Author: Wesley H. Self, MD, MPH, Department of Emergency Medicine, Vanderbilt University Medical Center, 1313 21st Ave S, Oxford House 312, Nashville, TN 37232 (wesley.self@vumc.org).
Accepted for Publication: October 26, 2020.
Published Online: November 9, 2020. doi:10.1001/jama.2020.22240
Author Contributions: Drs Schoenfeld and Hayden had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Schoenfeld and Self take responsibility for the trial overall.
Concept and design: Self, Semler, Angus, Casey, Brower, Collins, Eppensteiner, Ginde, Gong, Johnson, Moss, Rice, Robinson, Schoenfeld, Shapiro, Steingrub, Weissman, Yealy, Thompson, Brown.
Acquisition, analysis, or interpretation of data: Self, Semler, Leither, Casey, Angus, Brower, Chang, Collins, Filbin, Files, Gibbs, Ginde, Gong, Harrell, Hayden, Hough, Johnson, Khan, Lindsell, Matthay, Park, Rice, Robinson, Schoenfeld, Steingrub, Ulysse, Weissman, Thompson, Brown.
Drafting of the manuscript: Self, Semler, Casey, Angus, Collins, Johnson, Khan, Matthay, Moss, Robinson, Shapiro, Steingrub, Ulysse, Weissman, Yealy, Thompson, Brown.
Critical revision of the manuscript for important intellectual content: Self, Semler, Leither, Casey, Angus, Brower, Chang, Collins, Eppensteiner, Filbin, Files, Gibbs, Ginde, Gong, Harrell, Hayden, Hough, Johnson, Schoenfeld, Khan, Lindsell, Matthay, Moss, Park, Rice, Robinson, Shapiro, Steingrub, Ulysse, Yealy, Thompson, Brown.
Statistical analysis: Semler, Casey, Angus, Gibbs, Harrell, Hayden, Lindsell, Schoenfeld, Steingrub, Ulysse.
Obtained funding: Self, Collins, Gong, Moss, Shapiro, Thompson.
Administrative, technical, or material support: Self, Semler, Casey, Angus, Ginde, Khan, Rice, Robinson, Shapiro, Thompson.
Supervision: Self, Semler, Casey, Angus, Brower, Chang, Collins, Ginde, Johnson, Moss, Rice, Robinson, Yealy, Thompson, Brown.
Conflict of Interest Disclosures: Dr Self reported receiving grants from the National Heart, Lung, and Blood Institute (NHLBI) during the conduct of the study and personal fees from Aerpio Pharmaceuticals outside the submitted work. Dr Semler reported receiving grants from the NHLBI during the conduct of the study. Dr Leither reported receiving grants from the NHLBI during the conduct of the study. Dr Casey reported receiving grants from the NHLBI during the conduct of the study. Dr Angus reported receiving grants from the NHLBI and National Center for Advancing Translational Sciences (NCATS) during the conduct of the study and personal fees from Ferring Pharmaceuticals, Bristol-Myers Squibb, and Bayer AG and stock from Alung Technologies. Dr Angus has patents pending through Ferring Pharmaceuticals and the University of Pittsburgh. Dr Chang reported receiving grants from the NHLBI during the conduct of the study and personal fees from PureTech Health and LaJolla Pharmaceuticals outside the submitted work. Dr Collins reported receiving grants from the NHLBI and personal fees from Vir Biotechnology outside the submitted work. Dr Filbin reported receiving grants from the NHLBI during the conduct of the study. Dr Files reported receiving grants from the NIH during the conduct of the study and personal fees from Cytovale and Medpace outside the submitted work. Dr Ginde reported receiving grants from the NIH during the conduct of the study. Dr Gong reported receiving grants from the NHLBI for the submitted work and research funding from the Agency for Healthcare Research and Quality and Regeneron outside the submitted work. Dr Harrell reported receiving grants from the NHLBI and the NCATS during the conduct of this study and personal fees from Adapt Health, Springer, Stanford, University of Texas, ICSB, Duke, Ottawa Hospital, American Statistical Association, Yale, Virginia Commonwealth University, and Arnold Foundation outside the submitted work. Dr Hough reported receiving grants from the NIH during the conduct of the study. Dr Khan reported receiving grants from GlaxoSmithKline, United Therapeutics, Reata Pharmaceuticals, Actelion Pharmaceuticals, and Lung LLC outside the submitted work. Dr Lindsell reported receiving grants from the NHLBI during the conduct of the study and grants from the Department of Defense, NCATS, the NHLBI, the Centers for Disease Control and Prevention, and Marcus Foundation; research contracts from Endpoint Health, Entegrion, and bioMerieux outside the submitted work; in addition, Dr Lindsell has a patent risk stratification in sepsis and septic shock issued. Dr Matthay reported receiving grants from the NHLBI during the conduct of the study and grants from Bayer Pharmaceuticals, Roche-Genentech, the Department of Defense, and the California Institute of Regenerative Medicine and personal fees from GEn1E LifeSciences, Citius Pharma, and Novartis outside the submitted work. Dr Moss reported receiving grants from the NHLBI during the conduct of the study. Dr Park reported receiving grants from NHLBI during the conduct of the study and grants from Eli Lilly and service on Council of the Society of Critical Care Medicine outside the submitted work. Dr Rice reported receiving grants from the NHLBI during the conduct of the study and personal fees from Cumberland Pharmaceuticals Inc, Avisa Pharmaceutical LLC consulting, and Cytovale Inc outside the submitted work. Dr Schoenfeld reported receiving grants from the NIH during the conduct of the study and personal fees from Immunity Pharma and Theravance outside the sumitted work. Dr Shapiro reported receiving grants from the NIH during the conduct of the study. Dr Steingrub reported receiving grants from the NHLBI during the conduct of the study. Dr Yealy reported receiving grants from the NHLBI during the conduct of the study and personal fees from McGraw Hill Inc, Lippincott Williams & Wilkins, Wolters Kluwer Inc, the American College of Emergency Physicians, multiple legal corporations, and UpToDate Inc outside the submitted work. Dr Thompson reported receiving grants from the NHLBI during the conduct of the study and personal fees from Bayer, Novartis, and Thetis outside the submitted work. Dr Brown reported receiving grants from the NHLBI during the conduct of the study and personal fees from Hamilton, Oxford University Press/Brigham Young University, and New York University and grants from Faron Pharmaceuticals, Sedana Pharmaceuticals, Janssen, the NIH, and Department of Defense outside the submitted work. No other disclosures were reported.
Funding/Support: This study was supported by grants from the NHLBI (3U01HL123009-06S1, U01HL123009, U01HL122998, U01HL123018, U01HL123023, U01HL123008, U01HL123031, U01HL123004, U01HL123027, U01HL123010, U01HL123033, U01HL122989, U01HL123022, and U01HL123020). The REDCap data tools used for this study were supported by a grant from NCATS (5UL1TR002243). The work at Massachusetts General Hospital was supported in part by the Harvard Catalyst/Harvard Clinical and Translational Science Center (NCATS, NIH awards UL1TR001102 and UL1TR002541-01). Sandoz, a Novartis division, supplied the hydroxychloroquine and placebo used in this trial.
Role of the Funders/Sponsor: The NHLBI supported the trial through funding, appointed a protocol review committee and data and safety monitoring board, and reviewed the manuscript prior to submission for publication but did not have the power to veto publication or select a journal. The NHLBI had no role in the design and conduct of the study; in the collection, management, analysis, and interpretation of the data; in the preparation of the manuscript; and in the decision to submit the manuscript for publication. Representatives from Sandoz reviewed the manuscript prior to submission for publication but did not have the power to veto publication or select a journal. Sandoz had no role in the design and conduct of the study; in the collection, management, analysis, and interpretation of the data; the preparation of the manuscript; and the decision to submit the manuscript for publication.
Disclaimer: Dr Angus is Senior Editor of JAMA, but he was not involved in any of the decisions regarding review of the manuscript or its acceptance.
Group Information: The National Heart, Lung, and Blood Institute PETAL Clinical Trials Network members are listed in the eAppendix in Supplement 3.
Data Sharing Statement: See Supplement 4.
Additional Information: The data analyses for this trial were conducted at the PETAL Clinical Trials Network Data Coordinating Center at Massachusetts General Hospital by Drs Schoenfeld and Hayden and Ms Ulysse.
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