Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials.
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2021-04-15
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Abstract
Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/ ). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I² = 0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I² = 0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.
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Axfors, Cathrine, Andreas M Schmitt, Perrine Janiaud, Janneke Van't Hooft, Sherief Abd-Elsalam, Ehab F Abdo, Benjamin S Abella, Javed Akram, et al. (2021). Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials. Nature communications, 12(1). p. 2349. 10.1038/s41467-021-22446-z Retrieved from https://hdl.handle.net/10161/23598.
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Scholars@Duke
Arthur Wakefield Baker
Thuy Le
Ahmad Mourad
Shanti Narayanasamy
Nwora Lance Okeke
Frank Wesley Rockhold
Frank is a full time Professor of Biostatistics and Bioinformatics and Faculty Director for Biostatistics at Duke University Medical Center, Affiliate Professor of Biostatistics at Virginia Commonwealth University, and Strategic Consultant at Hunter Rockhold, Inc. His 40+-year career includes senior research positions at Lilly, Merck, and GlaxoSmithKline, where he retired as Chief Safety Officer and Senior Vice President of Global Clinical Safety and Pharmacovigilance. He has held faculty appointments at six different universities. Dr. Rockhold served for 9 years on the board of directors of the non-profit CDISC, most recently as Chairman, and is past president of the Society for Clinical Trials and a past member of the PCORI Clinical Trials Advisory Panel. He is currently Chair of the Board of the Frontier Science and Technology Research Foundation and a technical advisor to EMA.
Dr. Rockhold has diverse research interests and consulting experience in industry and academia including clinical trials design, data monitoring, benefit/risk, safety and pharmacovigilance and has been a leader in the scientific community in promoting data disclosure and transparency in clinical research. Frank is widely published in major scientific journals across a wide variety of research topics.
Frank holds a BA in Statistics from The University of Connecticut, an ScM in Biostatistics from The Johns Hopkins University, and a PhD in Biostatistics from the Medical College of Virginia at Virginia Commonwealth University. Frank is an Elected Fellow of both the American Statistical Association and the Society for Clinical Trials, a Fellow of the Royal Statistical Society, an Accredited Professional Statistician, PStat®, and a Chartered Statistician, CStat.
Jason Eric Stout
My research focuses on the epidemiology, natural history, and treatment of tuberculosis and nontuberculous mycobacterial infections. I am also interested in the impact of HIV infection on mycobacterial infection and disease, and in examining health disparities as they relate to infectious diseases, particularly in immigrant populations.
Nicholas Turner
Rebekah Wrenn
Board-Certified Infectious Diseases Clinical Pharmacist with over 14 years of experience in both community and academic healthcare settings. Highly results-driven, with a proven track record in building and leading high-performing, innovative teams that deliver measurable improvements in patient care outcomes. Subject matter expert in infectious diseases pharmacotherapy, with an interest in cutting-edge microbiology technologies and the application of artificial intelligence (AI) into healthcare, to enhance decision-making and streamline antimicrobial stewardship practices.
My career began in HIV research at GlaxoSmithKline, where I honed my analytical skills in the pharmaceutical industry. I then pursued a Doctor of Pharmacy degree at UNC Eshelman School of Pharmacy, followed by completing a pharmacy practice residency and a specialty residency in infectious diseases pharmacotherapy at Wake Forest Baptist Health. Since completing my residency, I have dedicated my career to advancing the field of Infectious Diseases and Antimicrobial Stewardship, with a particular focus on incorporating innovative strategies to improve patient care. I currently serve as the Manager of Infectious Diseases Pharmacy Services, where I lead multidisciplinary antimicrobial stewardship and ambulatory Infectious Diseases programs, guide formulary decisions, and optimize patient outcomes, and ensure regulatory compliance. I've built successful teams, implemented cutting-edge stewardship strategies, and driven meaningful reductions in antimicrobial utilization.
I am an active committee member and speaker for prominent national and local professional societies, including the Society of Infectious Diseases Pharmacists (SIDP), the Infectious Diseases Society of America (IDSA), and the Society for Healthcare Epidemiology of America (SHEA). My contributions to these organizations reflect my commitment to staying at the forefront of the field and driving continuous improvement in healthcare practices.
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