Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials
Por:
Axfors C., Schmitt A.M., Janiaud P., van’t Hooft J., Abd-Elsalam S., Abdo E.F., Abella B.S., Akram J., Amaravadi R.K., Angus D.C., Arabi Y.M., Azhar S., Baden L.R., Baker A.W., Belkhir L., Benfield T., Berrevoets M.A.H., Chen C.-P., Chen T.-C., Cheng S.-H., Cheng C.-Y., Chung W.-S., Cohen Y.Z., Cowan L.N., Dalgard O., de Almeida e Val F.F., de Lacerda M.V.G., de Melo G.C., Derde L., Dubee V., Elfakir A., Gordon A.C., Hernandez-Cardenas C.M., Hills T., Hoepelman A.I.M., Huang Y.-W., Igau B., Jin R., Jurado-Camacho F., Khan K.S., Kremsner P.G., Kreuels B., Kuo C.-Y., Le T., Lin Y.-C., Lin W.-P., Lin T.-H., Lyngbakken M.N., McArthur C., McVerry B.J., Meza-Meneses P., Monteiro W.M., Morpeth S.C., Mourad A., Mulligan M.J., Murthy S., Naggie S., Narayanasamy S., Nichol A., Novack L.A., O’Brien S.M., Okeke N.L., Perez L., Perez-Padilla R., Perrin L., Remigio-Luna A., Rivera-Martinez N.E., Rockhold F.W., Rodriguez-Llamazares S., Rolfe R., Rosa R., Røsjø H., Sampaio V.S., Seto T.B., Shehzad M., Soliman S., Stout J.E., Thirion-Romero I., Troxel A.B., Tseng T.-Y., Turner N.A., Ulrich R.J., Walsh S.R., Webb S.A., Weehuizen J.M., Velinova M., Wong H.-L., Wrenn R., Zampieri F.G., Zhong W., Moher D., Goodman S.N., Ioannidis J.P.A., Hemkens L.G.
Publicada:
1 ene 2021
Resumen:
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of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished.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 We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed,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. © 2021, The Author(s).
Filiaciones:
Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, CA, United States
Department for Women’s and Children’s Health, Uppsala University, Uppsala, Sweden
Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland
Department of Medical Oncology, University of Basel, Basel, Switzerland
Amsterdam University Medical Center, Amsterdam University, Amsterdam, Netherlands
Tropical Medicine and Infectious Diseases Department, Faculty of Medicine, Tanta University, Tanta, Egypt
Tropical Medicine and Gastroenterology Department, Faculty of Medicine, Assiut University, Assiut, Egypt
Department of Emergency Medicine, University of Pennsylvania, Philadelphia, PA, United States
Department of Internal Medicine, Vice Chancellor, University of Health Sciences, Lahore, Punjab, Pakistan
Abramson Cancer Center and Department of Medicine, University of Pennsylvania, Philadelphia, PA, United States
Department of Critical Care Medicine, The Clinical Research Investigation and Systems Modeling of Acute Illness (CRISMA) Center, University of Pittsburgh, Pittsburgh, PA, United States
the UPMC Health System Office of Healthcare Innovation, University of Pittsburgh Medical Centre, Pittsburgh, PA, United States
Intensive Care Department, King Saud Bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
Department of Public Health, University of Health Sciences, Lahore, Punjab, Pakistan
Division of Infectious Diseases, Brigham and Women’s Hospital, Boston, MA, United States
Department of Medicine, Division of Infectious Diseases and International Health, Duke University Medical Center, Durham, NC, United States
Infectious Diseases Department, Cliniques universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium
Center of Research & Disruption of Infectious Diseases, Department of Infectious Diseases, Copenhagen University Hospital, Amager and Hvidovre, Hvidovre, Denmark
Department of Internal Medicine, Elisabeth-Tweesteden hospital, Tilburg, Netherlands
Department of Infectious Diseases, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan
Department of Internal Medicine, Taichung Hospital, Ministry of Health and Welfare, Taichung, Taiwan
Sanofi, Bridgewater, NJ, United States
Department of Infectious Diseases, Division of Medicine, Akershus University Hospital, Lørenskog, Norway
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
Division of Medicine, Akershus University Hospital, Lørenskog, Norway
Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, AM, Brazil
Instituto Leonidas e Maria Deane – ILMD, FIOCRUZ-AM, Manaus, AM, Brazil
Universidade do Estado do Amazonas, Manaus, AM, Brazil
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands
Intensive Care Centre, University Medical Center Utrecht, Utrecht, Netherlands
Infectious and Tropical Diseases Department, Angers University Hospital, Angers, France
Ividata Life Sciences, Levallois-Perret, France
Department of Surgery and Cancer, Anaesthetics, Pain Medicine, and Intensive Care Medicine, Imperial College London and Imperial College Healthcare NHS Trust, London, United Kingdom
Critical Care Department, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Ciudad de México, Mexico
Medical Research Institute of New Zealand, Wellington, New Zealand
Auckland City Hospital, Auckland, New Zealand
Department of Infectious Diseases, University Medical Center Utrecht, Utrecht, Netherlands
Department of Internal Medicine, Chang Hua Hospital, Ministry of Health and Welfare, Changhua, Taiwan
Beijing Youan Hospital, Capital Medical University, Beijing, China
Department of Preventive Medicine & Public Health, University of Granada, Hospital Real, Avenida del Hospicio, Granada, Granada, Spain
Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon
German Center for Infection Research, Partner Site Tübingen, Tübingen, Germany
Department of Medicine, Division of Tropical Medicine and Division of Infectious Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Department of Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany
Department of Internal Medicine, Pingtung Hospital, Ministry of Health and Welfare, Pingtung, Taiwan
Department of Internal Medicine, Taipei Hospital, Ministry of Health and Welfare, New Taipei City, Taiwan
School of Epidemiology and Preventive Medicine, Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, VIC, Australia
Department of Medicine, University of Pittsburgh, Pittsburgh, PA, United States
Hospital Regional de Alta Especialidad de Ixtapaluca, Ixtapaluca, Mexico
Middlemore Hospital, Auckland, New Zealand
Department of Medicine, Duke University Medical Center, Durham, NC 27710, United States
Department of Microbiology, NYU Grossman School of Medicine, New York, NY, United States
Department of Internal Medicine, Division of Infectious Diseases and Immunology, NYU Grossman School of Medicine, New York, NY, United States
University of British Columbia School of Medicine, Vancouver, BC, Canada
Department of Intensive Care, Alfred Health, Melbourne, VIC, Australia
Department of Anesthesia and Intensive Care, St Vincent’s University Hospital, Dublin, Ireland
School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland
Division of Infectious Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
Department of Biostatistics and Bioinformatics, Duke University Medical Center and Duke Clinical Research Institute, Durham, NC, United States
Excelya, Montpellier, France
Department of Smoking and COPD, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Ciudad de México, Mexico
Sanofi, Montpellier, France
Hospital Regional de Alta especialidad de Oaxaca, Oaxaca, Mexico
UnityPoint Health, Des Moines, IA, United States
Division of Research and Innovation, Akershus University Hospital, Lørenskog, Norway
Fundação de Vigilância em Saúde do Amazonas, Manaus, AM, Brazil
University of Hawaii John A. Burns School of Medicine, Honolulu, HI, United States
The Queen’s Medical Center, Honolulu, HI, United States
Department of Pharmacology, University of Health Sciences, Lahore, Punjab, Pakistan
Public Health and Community Medicine, Menoufia University, Menoufia, Egypt
Division of Biostatistics, Department of Population Health, NYU Grossman School of Medicine, New York, NY, United States
Department of Medicine, Division of Infectious Diseases and Immunology, NYU Grossman School of Medicine, New York, NY, United States
St. John of God Hospital, Subiaco, WA, Australia
PRA Health Science, Groningen, Netherlands
Department of Internal Medicine, Keelung Hospital, Ministry of Health and Welfare, Keelung, Taiwan
Research Institute, HCor-Hospital do Coração, São Paulo, Brazil
Research Institute, BRICNet - Brazilian Research in Intensive Care Network, São Paulo, Brazil
IDor Research Institute, São Paulo, Brazil
National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing, China
Centre for Journalology, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada
Stanford University School of Medicine, Stanford, CA, United States
Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA, United States
Stanford Prevention Research Center, Department of Medicine, Stanford University, Stanford, CA, United States
Meta-Research Innovation Center Berlin (METRIC-B), Berlin Institute of Health, Berlin, Germany
All Open Access, Gold
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