| Literature DB >> 33859192 |
Cathrine Axfors1,2, Andreas M Schmitt3,4, Perrine Janiaud3, Janneke Van't Hooft1,5, Sherief Abd-Elsalam6, Ehab F Abdo7, Benjamin S Abella8, Javed Akram9, Ravi K Amaravadi10, Derek C Angus11,12, Yaseen M Arabi13, Shehnoor Azhar14, Lindsey R Baden15, Arthur W Baker16, Leila Belkhir17, Thomas Benfield18, Marvin A H Berrevoets19, Cheng-Pin Chen20, Tsung-Chia Chen21, Shu-Hsing Cheng20, Chien-Yu Cheng20, Wei-Sheng Chung21, Yehuda Z Cohen22, Lisa N Cowan22, Olav Dalgard23,24, Fernando F de Almeida E Val25, Marcus V G de Lacerda25,26, Gisely C de Melo25,27, Lennie Derde28,29, Vincent Dubee30, Anissa Elfakir31, Anthony C Gordon32, Carmen M Hernandez-Cardenas33, Thomas Hills34,35, Andy I M Hoepelman36, Yi-Wen Huang37, Bruno Igau22, Ronghua Jin38, Felipe Jurado-Camacho33, Khalid S Khan39, Peter G Kremsner40,41,42, Benno Kreuels43,44, Cheng-Yu Kuo45, Thuy Le16, Yi-Chun Lin20, Wu-Pu Lin46, Tse-Hung Lin37, Magnus Nakrem Lyngbakken24,47, Colin McArthur34,35,48, Bryan J McVerry49, Patricia Meza-Meneses50, Wuelton M Monteiro25,27, Susan C Morpeth51, Ahmad Mourad52, Mark J Mulligan53,54, Srinivas Murthy55, Susanna Naggie16, Shanti Narayanasamy16, Alistair Nichol48,56,57,58, Lewis A Novack59, Sean M O'Brien60, Nwora Lance Okeke16, Léna Perez61, Rogelio Perez-Padilla62, Laurent Perrin63, Arantxa Remigio-Luna62, Norma E Rivera-Martinez64, Frank W Rockhold60, Sebastian Rodriguez-Llamazares62, Robert Rolfe16, Rossana Rosa65, Helge Røsjø24,66, Vanderson S Sampaio25,67, Todd B Seto68,69, Muhammad Shehzad70, Shaimaa Soliman71, Jason E Stout16, Ireri Thirion-Romero62, Andrea B Troxel72, Ting-Yu Tseng21, Nicholas A Turner16, Robert J Ulrich73, Stephen R Walsh15, Steve A Webb48,74, Jesper M Weehuizen36, Maria Velinova75, Hon-Lai Wong76, Rebekah Wrenn16, Fernando G Zampieri77,78,79, Wu Zhong80, David Moher81, Steven N Goodman1,82,83, John P A Ioannidis1,82,83,84,85, Lars G Hemkens86,87,88.
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of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished.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.Entities:
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Year: 2021 PMID： 33859192 DOI： 10.1038/s41467-021-22446-z
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919