Dataset Information

Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials.

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of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished.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 We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed,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 We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients).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.

SUBMITTER: Axfors C

PROVIDER: S-EPMC8050319 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials.

Axfors Cathrine C Schmitt Andreas M AM Janiaud Perrine P Van't Hooft Janneke J Abd-Elsalam Sherief S Abdo Ehab F EF Abella Benjamin S BS Akram Javed J Amaravadi Ravi K RK Angus Derek C DC Arabi Yaseen M YM Azhar Shehnoor S Baden Lindsey R LR Baker Arthur W AW Belkhir Leila L Benfield Thomas T Berrevoets Marvin A H MAH Chen Cheng-Pin CP Chen Tsung-Chia TC Cheng Shu-Hsing SH Cheng Chien-Yu CY Chung Wei-Sheng WS Cohen Yehuda Z YZ Cowan Lisa N LN Dalgard Olav O de Almeida E Val Fernando F FF de Lacerda Marcus V G MVG de Melo Gisely C GC Derde Lennie L Dubee Vincent V Elfakir Anissa A Gordon Anthony C AC Hernandez-Cardenas Carmen M CM Hills Thomas T Hoepelman Andy I M AIM Huang Yi-Wen YW Igau Bruno B Jin Ronghua R Jurado-Camacho Felipe F Khan Khalid S KS Kremsner Peter G PG Kreuels Benno B Kuo Cheng-Yu CY Le Thuy T Lin Yi-Chun YC Lin Wu-Pu WP Lin Tse-Hung TH Lyngbakken Magnus Nakrem MN McArthur Colin C McVerry Bryan J BJ Meza-Meneses Patricia P Monteiro Wuelton M WM Morpeth Susan C SC Mourad Ahmad A Mulligan Mark J MJ Murthy Srinivas S Naggie Susanna S Narayanasamy Shanti S Nichol Alistair A Novack Lewis A LA O'Brien Sean M SM Okeke Nwora Lance NL Perez Léna L Perez-Padilla Rogelio R Perrin Laurent L Remigio-Luna Arantxa A Rivera-Martinez Norma E NE Rockhold Frank W FW Rodriguez-Llamazares Sebastian S Rolfe Robert R Rosa Rossana R Røsjø Helge H Sampaio Vanderson S VS Seto Todd B TB Shahzad Muhammad M Soliman Shaimaa S Stout Jason E JE Thirion-Romero Ireri I Troxel Andrea B AB Tseng Ting-Yu TY Turner Nicholas A NA Ulrich Robert J RJ Walsh Stephen R SR Webb Steve A SA Weehuizen Jesper M JM Velinova Maria M Wong Hon-Lai HL Wrenn Rebekah R Zampieri Fernando G FG Zhong Wu W Moher David D Goodman Steven N SN Ioannidis John P A JPA Hemkens Lars G LG

Nature communications 20210415 1

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 COV ...[more]

PMID: 33859192

Similar Datasets

Project description:The coronavirus disease 19 (COVID-19) pandemic has caused significant morbidity and mortality worldwide and an effective treatment is needed. Chloroquine (CQ) and hydroxychloroquine (HCQ) have shown in vitro antiviral activity against SARS-CoV-2 which causes the disease, but the evidence from in vivo studies so far has been inconclusive.ObjectiveTo evaluate the efficacy and safety of CQ and HCQ in the treatment of COVID-19.Data sourcesWe systematically searched the PubMed, Embase, MEDLINE, Cochrane CENTRAL, CINAHL, Scopus, Joanna Briggs Institute Database, ClinicalTrials.gov, and Chinese Clinical Trial Registry (ChiCTR) for all articles published between 01 January 2020 to 15 September 2020 on CQ/HCQ and COVID-19 using a predefined search protocol; without any language restrictions. A search of grey literature repositories (New York Academy of Medicine Grey Literature and Open Grey), and pre-publication server deposits (medRxIV and bioRxIV) was also performed.Study selectionRandomized clinical trials (RCT) which compared CQ/HCQ to standard supportive therapy in treating COVID-19 were included.Data extraction and synthesisData were extracted from original publications by four independent reviewers. Risk of bias was assessed using the Cochrane Collaboration's assessment tool. Data were meta-analyzed using a random-effect models. Results are reported according to PRISMA guidelines. Main Outcome(s) and Measure(s): The primary prespecified efficacy outcome was all-cause mortality. The primary safety outcome was any adverse effect attributed to use of CQ/HCQ.ResultsEight RCTs were included and pooled in the mortality meta-analysis (6,592 unique participants; mean age = 59.4 years; 42% women). CQ/HCQ did not show any mortality benefit when compared to standard supportive therapy (Pooled Relative Risk [RR] 1.07; 95% CI = 0.97-1.18; I2 statistic = 0.00%). Sensitivity and sub-group analyses showed similar findings. Any adverse event was significantly higher in patients randomized to CQ/HCQ (RR = 2.51; 95% CI = 1.53-4.12; n = 1,818 patients), but the risk of developing severe adverse event was not statistically significant (RR = 0.99, 95% CI = 0.53-1.86; n = 6,456 patients).Conclusions and relevanceEvidence from currently published RCTs do not demonstrate any added benefit for the use of CQ or HCQ in the treatment of COVID-19 patients.

Project description:BackgroundConvalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ).MethodsIn this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence.ResultsA total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis.ConclusionsConvalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.

Dataset Information

Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials.

Publications

Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets