Author | Axfors, Cathrine | |
Author | Schmitt, Andreas M. | |
Author | Janiaud, Perrine | |
Author | Hooft, Janneke van’t | |
Author | Abd-Elsalam, Sherief | |
Author | Abdo, Ehab F. | |
Author | Abella, Benjamin S. | |
Author | Akram, Javed | |
Author | Amaravadi, Ravi K. | |
Author | Angus, Derek C. | |
Author | Arabi, Yaseen M. | |
Author | Azhar, Shehnoor | |
Author | Baden, Lindsey R. | |
Author | Baker, Arthur W. | |
Author | Belkhir, Leila | |
Author | Benfield, Thomas | |
Author | Berrevoets, Marvin A. H. | |
Author | Chen, Cheng-Pin | |
Author | Chen, Tsung-Chia | |
Author | Cheng, Shu-Hsing | |
Author | Cheng, Chien-Yu | |
Author | Chung, Wei-Sheng Chung | |
Author | Cohen, Yehuda Z. Cohen | |
Author | Cowan, Lisa N. | |
Author | Dalgard, Olav | |
Author | Val, Fernando F. de Almeida e | |
Author | Lacerda, Marcus V. G. de | |
Author | Melo, Gisely C. de | |
Author | Derde, Lennie | |
Author | Dubee, Vincent | |
Author | Elfakir, Anissa | |
Author | Gordon, Anthony C. | |
Author | Hernandez-Cardenas, Carmen M. | |
Author | Hills, Thomas | |
Author | Hoepelman, Andy I. M. | |
Author | Huang, Yi-Wen | |
Author | Igau, Bruno | |
Author | Jin, Ronghua | |
Author | Jurado-Camacho, Felipe | |
Author | Khan, Khalid S. | |
Author | Kremsner, Peter G. | |
Author | Kreuels, Benno | |
Author | Kuo, Cheng-Yu | |
Author | Le, Thuy | |
Author | Lin, Yi-Chun | |
Author | Lin, Wu-Pu | |
Author | Lin, Tse-Hung | |
Author | Lyngbakken, Magnus Nakrem Lyngbakken | |
Author | McArthur, Colin | |
Author | McVerry, Bryan J. | |
Author | Meza-Meneses, Patricia | |
Author | Monteiro, Wuelton M. | |
Author | Morpeth, Susan C. | |
Author | Mourad, Ahmad | |
Author | Mulligan, Mark J. | |
Author | Murthy, Srinivas | |
Author | Naggie, Susanna | |
Author | Narayanasamy, Shanti | |
Author | Nichol, Alistair | |
Author | Novack, Lewis A. | |
Author | O’Brien, Sean M. | |
Author | Okeke, Nwora Lance | |
Author | Perez, Léna | |
Author | Perez-Padilla, Rogelio | |
Author | Perrin, Laurent | |
Author | Remigio-Luna, Arantxa | |
Author | Rivera-Martinez, Norma E. | |
Author | Rockhold, Frank W. | |
Author | Rodriguez-Llamazares, Sebastian | |
Author | Rolfe, Robert | |
Author | Rosa, Rossana | |
Author | Røsjø, Helge | |
Author | Sampaio, Vanderson S. | |
Author | Seto, Todd B. | |
Author | Shahzad, Muhammad | |
Author | Soliman, Shaimaa | |
Author | Stout, Jason E. | |
Author | Thirion-Romero, Ireri | |
Author | Troxel, Andrea B. | |
Author | Tseng, Ting-Yu | |
Author | Turner, Nicholas A. | |
Author | Ulrich, Robert J. | |
Author | Walsh, Stephen R. | |
Author | Webb, Steve A. | |
Author | Weehuizen, Jesper M. | |
Author | Velinova, Maria | |
Author | Wong, Hon-Lai | |
Author | Wrenn, Rebekah | |
Author | Zampieri, Fernando G. | |
Author | Zhong, Wu | |
Author | Moher, David | |
Author | Goodman, Steven N. | |
Author | Ioannidis, John P. A. | |
Author | Hemkens, Lars G. | |
Access date | 2022-03-17T14:23:29Z | |
Available date | 2022-03-17T14:23:29Z | |
Document date | 2021 | |
Citation | AXFORS, Cathrine et al. Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials. Nature Communications, [s. l.], v. 12, n. 2349, p. 1-13, 2021. | pt_BR |
ISSN | 2041-1723 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/51720 | |
Description | Inclui correção do autor. | pt_BR |
Abstract in Portuguese | Investimento substancial em pesquisa COVID-19 foi alocado para ensaios clínicos randomizados (ECRs) sobre hidroxicloroquina/cloroquina, que atualmente enfrentam desafios de recrutamento ou descontinuação precoce. Nosso objetivo é estimar os efeitos da hidroxicloroquina e da cloroquina sobre a sobrevivência em COVID-19 de todas as evidências de RCT atualmente disponíveis, publicadas e não publicadas. Apresentamos uma rápida meta-análise de ECRs em andamento, concluídos ou descontinuados em tratamento com hidroxicloroquina ou cloroquina para qualquer paciente com COVID-19 (protocolo: : https://osf.io/QESV4/). Identificamos sistematicamente ECRs não publicados (ClinicalTrials.gov, WHO Plataforma Internacional de Registro de Ensaios Clínicos, registro Cochrane COVID até 11 de junho de 2020), e ECRs publicados (PubMed, medRxiv e bioRxiv até 16 de outubro de 2020). Todas as causas mortalidade foi extraída (publicações/pré-impressões) ou solicitada aos investigadores e combinados em meta-análises de efeitos aleatórios, calculando odds ratio (ORs) com intervalos de confiança de 95% (ICs), separadamente para hidroxicloroquina e cloroquina. Pré-especificado as análises de subgrupo incluem configuração do paciente, confirmação de diagnóstico, tipo de controle e status de publicação. Sessenta e três estudos eram potencialmente elegíveis. Incluímos 14 ensaios não publicados (1308 pacientes) e 14 publicações/preprints (9011 pacientes). Resultados para hidroxicloroquina são dominados por RECOVERY e WHO SOLIDARITY, dois ensaios altamente pragmáticos, que empregaram doses relativamente altas e incluíram 4.716 e 1.853 pacientes, respectivamente (67% dos o tamanho total da amostra). O OR combinado na mortalidade por todas as causas para hidroxicloroquina é 1,11 (IC 95%: 1,02, 1,20; I² = 0%; 26 ensaios; 10.012 pacientes) e para cloroquina 1,77 (IC 95%: 0,15, 21,13, I² = 0%; 4 ensaios; 307 pacientes). Não identificamos efeitos de subgrupo. Nós achamos isso tratamento com hidroxicloroquina está associado ao aumento da mortalidade na COVID-19 pacientes, e não há benefício da cloroquina. Os achados não têm generalização clara para ambulatorial, crianças, gestantes e pessoas com comorbidades. | pt_BR |
Language | eng | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | COVID-19 | pt_BR |
Subject in Portuguese | Hidroxicloroquina | pt_BR |
Subject in Portuguese | Cloroquina | pt_BR |
Title | Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials | pt_BR |
Type | Article | pt_BR |
DOI | 10.1038/s41467-021-22446-z | |
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. | pt_BR |
Affilliation | Stanford University. Meta-Research Innovation Center at Stanford (METRICS). Califórnia, CA, USA. | pt_BR |
Affilliation | University of Basel. University Hospital Basel. Department of Clinical Research. Basel, Switzerland. | pt_BR |
Affilliation | University of Basel. University Hospital Basel. Department of Clinical Research. Basel, Switzerland. | pt_BR |
Affilliation | Stanford University. Meta-Research Innovation Center at Stanford (METRICS). Califórnia, CA, USA. | pt_BR |
Affilliation | Tanta University. Faculty of Medicine. Tropical Medicine and Infectious Diseases Department. Tanta, Egypt. | pt_BR |
Affilliation | Assiut University. Faculty of Medicine. Tropical Medicine and Gastroenterology Department. Assiut, Egypt. | pt_BR |
Affilliation | University of Pennsylvania. Department of Emergency Medicine. Philadelphia, PA, USA. | pt_BR |
Affilliation | University of Health Sciences. Vice Chancellor. Department of Internal Medicine. Lahore, Punjab, Pakistan. | pt_BR |
Affilliation | University of Pennsylvania. Abramson Cancer Center and Department of Medicine. Philadelphia, PA, USA. | pt_BR |
Affilliation | University of Pittsburgh. Department of Critical Care Medicine. The Clinical Research Investigation and Systems Modeling of Acute Illness (CRISMA) Center. Pittsburgh, PA, USA. | pt_BR |
Affilliation | Intensive Care Department. King Saud Bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center. Riyadh, Saudi Arabia. | pt_BR |
Affilliation | University of Health Sciences. Department of Public Health. Lahore, Punjab, Pakistan. | pt_BR |
Affilliation | Division of Infectious Diseases. Brigham and Women’s Hospital. Boston, MA, USA. | pt_BR |
Affilliation | Duke University Medical Center. Department of Medicine. Division of Infectious Diseases and International Health. Durham, NC, USA. | pt_BR |
Affilliation | Université Catholique de Louvain. Infectious Diseases Department. Cliniques universitaires Saint-Luc. Brussels, Belgium. | pt_BR |
Affilliation | Copenhagen University Hospital. Center of Research & Disruption of Infectious Diseases. Department of Infectious Diseases. Amager and Hvidovre. Hvidovre, Denmark. | pt_BR |
Affilliation | Elisabeth-Tweesteden hospital. Department of Internal Medicine. Tilburg, Netherlands. | pt_BR |
Affilliation | Department of Infectious Diseases. Taoyuan General Hospital. Ministry of Health and Welfare. Taoyuan, Taiwan. | pt_BR |
Affilliation | Department of Internal Medicine. Taichung Hospital. Ministry of Health and Welfare. Taichung, Taiwan. | pt_BR |
Affilliation | Department of Infectious Diseases. Taoyuan General Hospital. Ministry of Health and Welfare. Taoyuan, Taiwan. | pt_BR |
Affilliation | Department of Infectious Diseases. Taoyuan General Hospital. Ministry of Health and Welfare. Taoyuan, Taiwan. | pt_BR |
Affilliation | Department of Internal Medicine. Taichung Hospital. Ministry of Health and Welfare. Taichung, Taiwan. | pt_BR |
Affilliation | Sanofi. Bridgewater. NJ, USA. | pt_BR |
Affilliation | Sanofi. Bridgewater. NJ, USA. | pt_BR |
Affilliation | Akershus University Hospital. Department of Infectious Diseases. Division of Medicine. Lørenskog, Norway. | pt_BR |
Affilliation | Fundação de Medicina Tropical Dr. Heitor Vieira Dourado. Manaus, AM, Brasil. | pt_BR |
Affilliation | Fundação de Medicina Tropical Dr. Heitor Vieira Dourado. Manaus, AM, Brasil / Fundação Oswaldo Cruz. Instituto Leonidas e Maria Deane. Manaus, AM, Brasil. | pt_BR |
Affilliation | Fundação de Medicina Tropical Dr. Heitor Vieira Dourado. Manaus, AM, Brasil. | pt_BR |
Affilliation | University Medical Center Utrecht. Julius Center for Health Sciences and Primary Care. Utrecht, Netherlands. | pt_BR |
Affilliation | Angers University Hospital. Infectious and Tropical Diseases Department. Angers, France. | pt_BR |
Affilliation | Ividata Life Sciences. Levallois-Perret, France. | pt_BR |
Affilliation | Department of Surgery and Cancer, Anaesthetics, Pain Medicine, and Intensive Care Medicine. Imperial College London and Imperial College Healthcare NHS Trust. London, UK. | pt_BR |
Affilliation | Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas. Critical Care Department. Ciudad de México, Mexico. | pt_BR |
Affilliation | Medical Research Institute of New Zealand. Wellington, New Zealand. | pt_BR |
Affilliation | University Medical Center Utrecht. Department of Infectious Diseases. Utrecht, Netherlands. | pt_BR |
Affilliation | Department of Internal Medicine. Chang Hua Hospital. Ministry of Health and Welfare. Changhua, Taiwan. | pt_BR |
Affilliation | Sanofi. Bridgewater. NJ, USA. | pt_BR |
Affilliation | Beijing Youan Hospital. Capital Medical University. Beijing, People’s Republic of China. | pt_BR |
Affilliation | Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas. Critical Care Department. Ciudad de México, Mexico. | pt_BR |
Affilliation | University of Granada. Hospital Real. Department of Preventive Medicine & Public Health. Avenida del Hospicio, Granada, Granada, Spain. | pt_BR |
Affilliation | University of Tübingen. Institute of Tropical Medicine. Tübingen, Germany. | pt_BR |
Affilliation | University Medical Center Hamburg-Eppendorf. Department of Medicine. Division of Tropical Medicine and Division of Infectious Diseases. Hamburg, Germany. | pt_BR |
Affilliation | Department of Internal Medicine. Pingtung Hospital. Ministry of Health and Welfare. Pingtung, Taiwan. | pt_BR |
Affilliation | Duke University Medical Center. Department of Medicine. Division of Infectious Diseases and International Health. Durham, NC, USA | pt_BR |
Affilliation | Department of Infectious Diseases. Taoyuan General Hospital. Ministry of Health and Welfare. Taoyuan, Taiwan. | pt_BR |
Affilliation | Department of Internal Medicine. Taipei Hospital. Ministry of Health and Welfare. New Taipei City, Taiwan | pt_BR |
Affilliation | Department of Internal Medicine. Chang Hua Hospital. Ministry of Health and Welfare. Changhua, Taiwan. | pt_BR |
Affilliation | University of Oslo. Faculty of Medicine. Institute of Clinical Medicine. Oslo, Norway. | pt_BR |
Affilliation | Medical Research Institute of New Zealand. Wellington, New Zealand. | pt_BR |
Affilliation | University of Pittsburgh. Department of Medicine. Pittsburgh, PA, USA. | pt_BR |
Affilliation | Hospital Regional de Alta especialidad de Ixtapaluca. Ixtapaluca, Mexico. | pt_BR |
Affilliation | Fundação de Medicina Tropical Dr. Heitor Vieira Dourado. Manaus, AM, Brasil. | pt_BR |
Affilliation | Middlemore Hospital. Auckland, New Zealand. | pt_BR |
Affilliation | Duke University Medical Center. Department of Medicine. Durham, NC, USA. | pt_BR |
Affilliation | NYU Grossman School of Medicine. Department of Microbiology. New York, NY, USA | pt_BR |
Affilliation | University of British Columbia School of Medicine. Vancouver, BC, Canada. | pt_BR |
Affilliation | Duke University Medical Center. Department of Medicine. Division of Infectious Diseases and International Health. Durham, NC, USA. | pt_BR |
Affilliation | Duke University Medical Center. Department of Medicine. Division of Infectious Diseases and International Health. Durham, NC, USA. | pt_BR |
Affilliation | Monash University. School of Epidemiology and Preventive Medicine. Australian and New Zealand Intensive Care Research Centre. Melbourne, VIC, Australia. | pt_BR |
Affilliation | Harvard Medical School. Division of Infectious Diseases. Brigham and Women’s Hospital. Boston, MA, USA. | pt_BR |
Affilliation | Duke University Medical Center and Duke Clinical Research Institute. Department of Biostatistics and Bioinformatics. Durham, NC, USA | pt_BR |
Affilliation | Duke University Medical Center. Department of Medicine. Division of Infectious Diseases and International Health. Durham, NC, USA. | pt_BR |
Affilliation | Excelya. Montpellier, France. | pt_BR |
Affilliation | Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas. Department of Smoking and COPD. Ciudad de México, Mexico. | pt_BR |
Affilliation | Sanofi. Montpellier, France. | pt_BR |
Affilliation | Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas. Department of Smoking and COPD. Ciudad de México, Mexico. | pt_BR |
Affilliation | Hospital Regional de Alta especialidad de Oaxaca. Oaxaca, Mexico. | pt_BR |
Affilliation | Duke University Medical Center and Duke Clinical Research Institute. Department of Biostatistics and Bioinformatics.Durham, NC, USA. | pt_BR |
Affilliation | Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas. Department of Smoking and COPD. Ciudad de México, Mexico. | pt_BR |
Affilliation | Duke University Medical Center. Department of Medicine. Division of Infectious Diseases and International Health. Durham, NC, USA. | pt_BR |
Affilliation | UnityPoint Health. Des Moines, IA, USA | pt_BR |
Affilliation | University of Oslo. Faculty of Medicine. Institute of Clinical Medicine. Oslo, Norway. | pt_BR |
Affilliation | Fundação de Medicina Tropical Dr. Heitor Vieira Dourado. Manaus, AM, Brasil. | pt_BR |
Affilliation | University of Hawaii John A. Burns School of Medicine. Honolulu, HI, USA. | pt_BR |
Affilliation | University of Health Sciences. Department of Pharmacology. Lahore, Punjab, Pakistan. | pt_BR |
Affilliation | Menoufia University. Public Health and Community Medicine. Menoufia, Egypt. | pt_BR |
Affilliation | Duke University Medical Center. Department of Medicine. Division of Infectious Diseases and International Health. Durham, NC, USA | pt_BR |
Affilliation | Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas. Department of Smoking and COPD. Ciudad de México, Mexico. | pt_BR |
Affilliation | NYU Grossman School of Medicine. Department of Population Health. Division of Biostatistics. New York, NY, USA. | pt_BR |
Affilliation | Department of Internal Medicine. Taichung Hospital. Ministry of Health and Welfare. Taichung, Taiwan. | pt_BR |
Affilliation | Duke University Medical Center. Department of Medicine. Division of Infectious Diseases and International Health. Durham, NC, USA. | pt_BR |
Affilliation | NYU Grossman School of Medicine. Department of Medicine. Division of Infectious Diseases and Immunology. New York, NY, USA. | pt_BR |
Affilliation | Brigham and Women’s Hospital. Division of Infectious Diseases. Boston, MA, USA. | pt_BR |
Affilliation | Monash University. School of Epidemiology and Preventive Medicine. Australian and New Zealand Intensive Care Research Centre. Melbourne, VIC, Australia. | pt_BR |
Affilliation | University Medical Center Utrecht. Department of Infectious Diseases. Utrecht, Netherlands. | pt_BR |
Affilliation | PRA Health Science. Groningen, Netherlands. | pt_BR |
Affilliation | Department of Internal Medicine. Keelung Hospital. Ministry of Health and Welfare. Keelung, Taiwan. | pt_BR |
Affilliation | Duke University Medical Center. Department of Medicine. Division of Infectious Diseases and International Health. Durham, NC, USA. | pt_BR |
Affilliation | Research Institute. HCor-Hospital do Coração. São Paulo, Brasil. | pt_BR |
Affilliation | National Engineering Research Center for the Emergency Drug. Beijing Institute of Pharmacology and Toxicology. Beijing, People’s Republic of China. | pt_BR |
Affilliation | Stanford University. Meta-Research Innovation Center at Stanford (METRICS). Califórnia, CA, USA. | pt_BR |
Affilliation | Stanford University. Meta-Research Innovation Center at Stanford (METRICS). Califórnia, CA, USA. | pt_BR |
Affilliation | Stanford University. Meta-Research Innovation Center at Stanford (METRICS). Califórnia, CA, USA. | pt_BR |
Subject | COVID-19 | pt_BR |
Subject | Hydroxychloroquine | pt_BR |
Subject | Chloroquine | pt_BR |
DeCS | COVID-19 | pt_BR |
DeCS | Hidroxicloroquina | pt_BR |