학술논문
Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials
Document Type
article
Author
Cathrine Axfors; Andreas M. Schmitt; Perrine Janiaud; Janneke van’t Hooft; Sherief Abd-Elsalam; Ehab F. Abdo; Benjamin S. Abella; Javed Akram; Ravi K. Amaravadi; Derek C. Angus; Yaseen M. Arabi; Shehnoor Azhar; Lindsey R. Baden; Arthur W. Baker; Leila Belkhir; Thomas Benfield; Marvin A. H. Berrevoets; Cheng-Pin Chen; Tsung-Chia Chen; Shu-Hsing Cheng; Chien-Yu Cheng; Wei-Sheng Chung; Yehuda Z. Cohen; Lisa N. Cowan; Olav Dalgard; Fernando F. de Almeida e Val; Marcus V. G. de Lacerda; Gisely C. de Melo; Lennie Derde; Vincent Dubee; Anissa Elfakir; Anthony C. Gordon; Carmen M. Hernandez-Cardenas; Thomas Hills; Andy I. M. Hoepelman; Yi-Wen Huang; Bruno Igau; Ronghua Jin; Felipe Jurado-Camacho; Khalid S. Khan; Peter G. Kremsner; Benno Kreuels; Cheng-Yu Kuo; Thuy Le; Yi-Chun Lin; Wu-Pu Lin; Tse-Hung Lin; Magnus Nakrem Lyngbakken; Colin McArthur; Bryan J. McVerry; Patricia Meza-Meneses; Wuelton M. Monteiro; Susan C. Morpeth; Ahmad Mourad; Mark J. Mulligan; Srinivas Murthy; Susanna Naggie; Shanti Narayanasamy; Alistair Nichol; Lewis A. Novack; Sean M. O’Brien; Nwora Lance Okeke; Léna Perez; Rogelio Perez-Padilla; Laurent Perrin; Arantxa Remigio-Luna; Norma E. Rivera-Martinez; Frank W. Rockhold; Sebastian Rodriguez-Llamazares; Robert Rolfe; Rossana Rosa; Helge Røsjø; Vanderson S. Sampaio; Todd B. Seto; Muhammad Shahzad; Shaimaa Soliman; Jason E. Stout; Ireri Thirion-Romero; Andrea B. Troxel; Ting-Yu Tseng; Nicholas A. Turner; Robert J. Ulrich; Stephen R. Walsh; Steve A. Webb; Jesper M. Weehuizen; Maria Velinova; Hon-Lai Wong; Rebekah Wrenn; Fernando G. Zampieri; Wu Zhong; David Moher; Steven N. Goodman; John P. A. Ioannidis; Lars G. Hemkens
Source
Nature Communications, Vol 12, Iss 1, Pp 1-13 (2021)
Subject
Language
English
ISSN
2041-1723
Abstract
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of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished.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.