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Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19: an international collaborative meta-analysis of randomized trials
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 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; Lena Perez; Rogelio Perez-Padilla; Laurent Perrin; Arantxa Remigio-Luna; Norma E Rivera-Martinez; Frank W Rockhold; Sebastian Rodriguez-Llamazares; Robert Rolfe; Rossana Rosa; Helge Rosjo; Vanderson S Sampaio; Todd B Seto; Muhammad Shehzad; 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.
Afiliación
  • Cathrine Axfors; Stanford University
  • Andreas M Schmitt; University of Basel
  • Perrine Janiaud; University of Basel
  • Janneke van 't Hooft; Amsterdam University
  • Sherief Abd-Elsalam; Tanta University
  • Ehab F Abdo; Assiut University
  • Benjamin S Abella; University of Pennsylvania
  • Javed Akram; University of Health Sciences, Lahore
  • Ravi K Amaravadi; University of Pennsylvania
  • Derek C Angus; University of Pittsburgh
  • Yaseen M Arabi; King Saud Bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center
  • Shehnoor Azhar; University of Health Sciences, Lahore
  • Lindsey R Baden; Brigham and Women's Hospital
  • Arthur W Baker; Duke University Medical Center
  • Leila Belkhir; Cliniques universitaires Saint-Luc, Universite Catholique de Louvain
  • Thomas Benfield; Copenhagen University Hospital, Amager and Hvidovre
  • Marvin A H Berrevoets; Elisabeth-Tweesteden hospital
  • Cheng-Pin Chen; Taoyuan General Hospital, Ministry of Health and Welfare
  • Tsung-Chia Chen; Taichung Hospital, Ministry of Health and Welfare
  • Shu-Hsing Cheng; Taoyuan General Hospital, Ministry of Health and Welfare
  • Chien-Yu Cheng; Taoyuan General Hospital, Ministry of Health and Welfare
  • Wei-Sheng Chung; Taichung Hospital, Ministry of Health and Welfare
  • Yehuda Z Cohen; Sanofi
  • Lisa N Cowan; Sanofi
  • Olav Dalgard; Akershus University Hospital
  • Fernando F de Almeida e Val; Fundacao de Medicina Tropical Dr. Heitor Vieira Dourado
  • Marcus V G de Lacerda; Fundacao de Medicina Tropical Dr. Heitor Vieira Dourado
  • Gisely C de Melo; Fundacao de Medicina Tropical Dr. Heitor Vieira Dourado
  • Lennie Derde; University Medical Center Utrecht
  • Vincent Dubee; Angers University Hospital
  • Anissa Elfakir; Ividata Life Sciences
  • Anthony C Gordon; Imperial College London and Imperial College Healthcare NHS Trust
  • Carmen M Hernandez-Cardenas; Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas
  • Thomas Hills; Medical Research Institute of New Zealand
  • Andy I M Hoepelman; University Medical Center Utrecht
  • Yi-Wen Huang; Chang Hua Hospital, Ministry of Health and Welfare
  • Bruno Igau; Sanofi
  • Ronghua Jin; Beijing Youan Hospital, Capital Medical University
  • Felipe Jurado-Camacho; Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas
  • Khalid S Khan; University of Granada
  • Peter G Kremsner; University of Tubingen
  • Benno Kreuels; University Medical Center Hamburg-Eppendorf
  • Cheng-Yu Kuo; Pingtung Hospital, Ministry of Health and Welfare
  • Thuy Le; Duke University Medical Center
  • Yi-Chun Lin; Taoyuan General Hospital, Ministry of Health and Welfare
  • Wu-Pu Lin; Taipei Hospital, Ministry of Health and Welfare
  • Tse-Hung Lin; Chang Hua Hospital, Ministry of Health and Welfare
  • Magnus Nakrem Lyngbakken; Akershus University Hospital
  • Colin McArthur; Medical Research Institute of New Zealand
  • Bryan McVerry; University of Pittsburgh
  • Patricia Meza-Meneses; Hospital Regional de Alta especialidad de Ixtapaluca
  • Wuelton M Monteiro; Fundacao de Medicina Tropical Dr. Heitor Vieira Dourado
  • Susan C Morpeth; Middlemore Hospital
  • Ahmad Mourad; Duke University Medical Center
  • Mark J Mulligan; NYU Grossman School of Medicine
  • Srinivas Murthy; University of British Columbia School of Medicine
  • Susanna Naggie; Duke University Medical Center
  • Shanti Narayanasamy; Duke University Medical Center
  • Alistair Nichol; Monash University
  • Lewis A Novack; Brigham and Women's Hospital, Harvard Medical School
  • Sean M O'Brien; Duke University Medical Center and Duke Clinical Research Institute
  • Nwora Lance Okeke; Duke University Medical Center
  • Lena Perez; Excelya
  • Rogelio Perez-Padilla; Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas
  • Laurent Perrin; Sanofi
  • Arantxa Remigio-Luna; Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas
  • Norma E Rivera-Martinez; Hospital Regional de Alta especialidad de Oaxaca
  • Frank W Rockhold; Duke University Medical Center and Duke Clinical Research Institute
  • Sebastian Rodriguez-Llamazares; Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas
  • Robert Rolfe; Duke University Medical Center
  • Rossana Rosa; UnityPoint Health
  • Helge Rosjo; Akershus University Hospital
  • Vanderson S Sampaio; Fundacao de Medicina Tropical Dr. Heitor Vieira Dourado
  • Todd B Seto; University of Hawaii John A. Burns School of Medicine
  • Muhammad Shehzad; University of Health Sciences, Lahore
  • Shaimaa Soliman; Menoufia University
  • Jason E Stout; Duke University Medical Center
  • Ireri Thirion-Romero; Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas
  • Andrea B Troxel; NYU Grossman School of Medicine
  • Ting-Yu Tseng; Taichung Hospital, Ministry of Health and Welfare
  • Nicholas A Turner; Duke University Medical Center
  • Robert J Ulrich; NYU Grossman School of Medicine
  • Stephen R Walsh; Brigham and Women's Hospital
  • Steve A Webb; Monash University
  • Jesper M Weehuizen; University Medical Center Utrecht
  • Maria Velinova; PRA Health Science
  • Hon-Lai Wong; Keelung Hospital, Ministry of Health and Welfare
  • Rebekah Wrenn; Duke University Medical Center
  • Fernando G Zampieri; HCor-Hospital do Coracao
  • Wu Zhong; National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology
  • David Moher; Ottawa Hospital Research Institute
  • Steven N Goodman; Stanford University
  • John P A Ioannidis; Stanford University
  • Lars G Hemkens; University of Basel
Preprint en En | PREPRINT-MEDRXIV | ID: ppmedrxiv-20194571
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 aimed to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We conducted 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 was 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 included 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 was 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 was associated with increased mortality in COVID-19 patients, and there was no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.
Licencia
cc_by_nc_nd
Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-MEDRXIV Tipo de estudio: Experimental_studies / Prognostic_studies / Rct / Review Idioma: En Año: 2020 Tipo del documento: Preprint
Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-MEDRXIV Tipo de estudio: Experimental_studies / Prognostic_studies / Rct / Review Idioma: En Año: 2020 Tipo del documento: Preprint