{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Axfors C"],"funding":["Swiss National Science Foundation","Svenska Läkaresällskapet","National Institute for Health Research (NIHR)","Uppsala Universitet","Lundbeck Foundation","Laura and John Arnold Foundation","Sweden-America Foundation"],"pagination":["2349"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8050319"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["12(1)"],"pubmed_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of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished.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 We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed,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 We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients).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."],"journal":["Nature communications"],"pubmed_title":["Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials."],"pmcid":["PMC8050319"],"funding_grant_id":["RP-2015-06-018","Covid-19 - REMAP-CAP","R349-2020-625"],"pubmed_authors":["Tseng TY","Murthy S","Meza-Meneses P","Dalgard O","Belkhir L","Troxel AB","O'Brien SM","Abd-Elsalam S","Narayanasamy S","Rivera-Martinez NE","Janiaud P","Cheng SH","Rockhold FW","Arabi YM","Amaravadi RK","Perrin L","Seto TB","Cowan LN","Remigio-Luna A","Van't Hooft J","Berrevoets MAH","McArthur C","Morpeth SC","Chen TC","Walsh SR","Thirion-Romero I","Gordon AC","Chen CP","Novack LA","Jin R","Ioannidis JPA","Kreuels B","Baden LR","Derde L","Jurado-Camacho F","Le T","Lin TH","Webb SA","Zhong W","Khan KS","Rolfe R","Weehuizen JM","Cheng CY","Lin YC","Schmitt AM","Elfakir A","Naggie S","Wrenn R","Wong HL","Baker AW","Benfield T","Mulligan MJ","Huang YW","Akram J","Lin WP","Dubee V","Velinova M","Angus DC","Chung WS","Mourad A","Rosjo H","Kuo CY","Abdo EF","de Melo GC","Lyngbakken MN","Turner NA","Azhar S","Okeke NL","Nichol A","McVerry BJ","Goodman SN","Perez L","Sampaio VS","Cohen YZ","Hoepelman AIM","Monteiro WM","Rosa R","Zampieri FG","Moher D","Abella BS","Ulrich RJ","Hernandez-Cardenas CM","Stout JE","Shahzad M","Hemkens LG","Hills T","de Lacerda MVG","Kremsner PG","Rodriguez-Llamazares S","Soliman S","Axfors C","de Almeida E Val FF","Perez-Padilla R","Igau B"],"additional_accession":[]},"is_claimable":false,"name":"Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials.","description":"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.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Apr","modification":"2024-11-20T17:48:31.266Z","creation":"2022-02-11T02:18:07.327Z"},"accession":"S-EPMC8050319","cross_references":{"pubmed":["33859192"],"doi":["10.1038/s41467-021-22446-z"]}}