Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials
Posted on 2021-11-21 - 04:24
Abstract Background Convalescent 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and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). Methods In 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 Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung–Knapp–Sidik–Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients).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 The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions Convalescent 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.
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Axfors, Cathrine; Janiaud, Perrine; Schmitt, Andreas M.; van’t Hooft, Janneke; Smith, Emily R.; Haber, Noah A.; et al. (2021). Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.5716841.v1
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AUTHORS (208)
CA
Cathrine Axfors
PJ
Perrine Janiaud
AS
Andreas M. Schmitt
Jv
Janneke van’t Hooft
ES
Emily R. Smith
NH
Noah A. Haber
AA
Akin Abayomi
MA
Manal Abduljalil
AA
Abdulkarim Abdulrahman
YA
Yeny Acosta-Ampudia
MA
Manuela Aguilar-Guisado
FA
Farah Al-Beidh
MA
Marissa M. Alejandria
RA
Rachelle N. Alfonso
MA
Mohammad Ali
MA
Manaf AlQahtani
AA
Alaa AlZamrooni
JA
Juan-Manuel Anaya
MA
Mark Angelo C. Ang
IA
Ismael F. Aomar