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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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of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished.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 We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed,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 We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients).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
Susanna Naggie
Dr. Susanna Naggie completed her undergraduate degrees in chemical engineering and biochemistry at the University of Maryland, College Park, and her medical education at Johns Hopkins School of Medicine. She conducted her internal medicine and infectious diseases fellowship training at Duke University Medical Center, where she also served as Chief Resident. She joined the faculty in the Duke School of Medicine in 2009. She is a Professor of Medicine and currently holds appointments at the Duke University School of Medicine, at the Duke Clinical Research Institute, and at the Durham Veterans Affairs Medical Center. Dr. Naggie is a clinical investigator with a focus in clinical trials in infectious diseases and translational research in HIV and liver disease. She is a standing member of the DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents and the CDC/NIH/IDSA-HIVMA Opportunistic Infections Guideline. She is the Vice Dean for Clinical and Translational Research and Director for the Duke Clinical and Translational Sciences Institute.
Shanti Narayanasamy
Sean Michael O'Brien
Statistical methods for healthcare provider profiling; observational studies; Bayesian data analysis.
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
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