Dataset Information

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

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and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ).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 Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence.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A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients).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 The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis.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.

SUBMITTER: Axfors C

PROVIDER: S-EPMC8605464 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Publications

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

Axfors Cathrine C Janiaud Perrine P Schmitt Andreas M AM Van't Hooft Janneke J Smith Emily R ER Haber Noah A NA Abayomi Akin A Abduljalil Manal M Abdulrahman Abdulkarim A Acosta-Ampudia Yeny Y Aguilar-Guisado Manuela M Al-Beidh Farah F Alejandria Marissa M MM Alfonso Rachelle N RN Ali Mohammad M AlQahtani Manaf M AlZamrooni Alaa A Anaya Juan-Manuel JM Ang Mark Angelo C MAC Aomar Ismael F IF Argumanis Luis E LE Averyanov Alexander A Baklaushev Vladimir P VP Balionis Olga O Benfield Thomas T Berry Scott S Birocco Nadia N Bonifacio Lynn B LB Bowen Asha C AC Bown Abbie A Cabello-Gutierrez Carlos C Camacho Bernardo B Camacho-Ortiz Adrian A Campbell-Lee Sally S Cao Damon H DH Cardesa Ana A Carnate Jose M JM Castillo German Jr J GJJ Cavallo Rossana R Chowdhury Fazle R FR Chowdhury Forhad U H FUH Ciccone Giovannino G Cingolani Antonella A Climacosa Fresthel Monica M FMM Compernolle Veerle V Cortez Carlo Francisco N CFN Costa Neto Abel A D'Antico Sergio S Daly James J Danielle Franca F Davis Joshua S JS De Rosa Francesco Giuseppe FG Denholm Justin T JT Denkinger Claudia M CM Desmecht Daniel D Díaz-Coronado Juan C JC Díaz Ponce-Medrano Juan A JA Donneau Anne-Françoise AF Dumagay Teresita E TE Dunachie Susanna S Dungog Cecile C CC Erinoso Olufemi O Escasa Ivy Mae S IMS Estcourt Lise J LJ Evans Amy A Evasan Agnes L M ALM Fareli Christian J CJ Fernandez-Sanchez Veronica V Galassi Claudia C Gallo Juan E JE Garcia Patricia J PJ Garcia Patricia L PL Garcia Jesus A JA Garigliany Mutien M Garza-Gonzalez Elvira E Gauiran Deonne Thaddeus V DTV Gaviria García Paula A PA Giron-Gonzalez Jose-Antonio JA Gómez-Almaguer David D Gordon Anthony C AC Gothot André A Grass Guaqueta Jeser Santiago JS Green Cameron C Grimaldi David D Hammond Naomi E NE Harvala Heli H Heralde Francisco M FM Herrick Jesica J Higgins Alisa M AM Hills Thomas E TE Hines Jennifer J Holm Karin K Hoque Ashraful A Hoste Eric E Ignacio Jose M JM Ivanov Alexander V AV Janssen Maike M Jennings Jeffrey H JH Jha Vivekanand V King Ruby Anne N RAN Kjeldsen-Kragh Jens J Klenerman Paul P Kotecha Aditya A Krapp Fiorella F Labanca Luciana L Laing Emma E Landin-Olsson Mona M Laterre Pierre-François PF Lim Lyn-Li LL Lim Jodor J Ljungquist Oskar O Llaca-Díaz Jorge M JM López-Robles Concepción C López-Cárdenas Salvador S Lopez-Plaza Ileana I Lucero Josephine Anne C JAC Lundgren Maria M Macías Juan J Maganito Sandy C SC Malundo Anna Flor G AFG Manrique Rubén D RD Manzini Paola M PM Marcos Miguel M Marquez Ignacio I Martínez-Marcos Francisco Javier FJ Mata Ana M AM McArthur Colin J CJ McQuilten Zoe K ZK McVerry Bryan J BJ Menon David K DK Meyfroidt Geert G Mirasol Ma Angelina L MAL Misset Benoît B Molton James S JS Mondragon Alric V AV Monsalve Diana M DM Moradi Choghakabodi Parastoo P Morpeth Susan C SC Mouncey Paul R PR Moutschen Michel M Müller-Tidow Carsten C Murphy Erin E Najdovski Tome T Nichol Alistair D AD Nielsen Henrik H Novak Richard M RM O'Sullivan Matthew V N MVN Olalla Julian J Osibogun Akin A Osikomaiya Bodunrin B Oyonarte Salvador S Pardo-Oviedo Juan M JM Patel Mahesh C MC Paterson David L DL Peña-Perez Carlos A CA Perez-Calatayud Angel A AA Pérez-Alba Eduardo E Perkina Anastasia A Perry Naomi N Pouladzadeh Mandana M Poyato Inmaculada I Price David J DJ Quero Anne Kristine H AKH Rahman Md M MM Rahman Md S MS Ramesh Mayur M Ramírez-Santana Carolina C Rasmussen Magnus M Rees Megan A MA Rego Eduardo E Roberts Jason A JA Roberts David J DJ Rodríguez Yhojan Y Rodríguez-Baño Jesús J Rogers Benjamin A BA Rojas Manuel M Romero Alberto A Rowan Kathryn M KM Saccona Fabio F Safdarian Mehdi M Santos Maria Clariza M MCM Sasadeusz Joe J Scozzari Gitana G Shankar-Hari Manu M Sharma Gorav G Snelling Thomas T Soto Alonso A Tagayuna Pedrito Y PY Tang Amy A Tatem Geneva G Teofili Luciana L Tong Steven Y C SYC Turgeon Alexis F AF Veloso Januario D JD Venkatesh Balasubramanian B Ventura-Enriquez Yanet Y Webb Steve A SA Wiese Lothar L Wikén Christian C Wood Erica M EM Yusubalieva Gaukhar M GM Zacharowski Kai K Zarychanski Ryan R Khanna Nina N Moher David D Goodman Steven N SN Ioannidis John P A JPA Hemkens Lars G LG

BMC infectious diseases 20211120 1

<h4>Background</h4>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 Scien ...[more]

PMID: 34800996

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Project description:Abstract Background: While passive immunotherapy has been considered beneficial for patients with severe respiratory viral infections, the treatment of COVID-19 cases with convalescent plasma produced mixed results. Thus, there is a lack of certainty and consensus regarding its effectiveness. This meta-analysis aims to assess the role of convalescent plasma treatment on the clinical outcomes of COVID-19 patients enrolled in randomized controlled trials (RCTs). Methods: A systematic search was conducted in the PubMed database (end-of-search: 29 December 2022) for RCTs on convalescent plasma therapy compared to supportive care\standard of care. Pooled relative risk (RR) and 95% confidence intervals were calculated with random-effects models. Subgroup and meta-regression analyses were also performed, in order to address heterogeneity and examine any potential association between the factors that varied, and the outcomes reported. The present meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: A total of 34 studies were included in the meta-analysis. Per overall analysis, convalescent plasma treatment was not associated with lower 28-day mortality [RR = 0.98, 95% CI (0.91, 1.06)] or improved 28-day secondary outcomes, such as hospital discharge [RR = 1.00, 95% CI (0.97, 1.03)], ICU-related or score-related outcomes, with effect estimates of RR = 1.00, 95% CI (0.98, 1.05) and RR = 1.06, 95% CI (0.95, 1.17), respectively. However, COVID-19 outpatients treated with convalescent plasma had a 26% less risk of requiring hospital care, when compared to those treated with the standard of care [RR = 0.74, 95% CI (0.56, 0.99)]. Regarding subgroup analyses, COVID-19 patients treated with convalescent plasma had an 8% lower risk of ICU-related disease progression when compared to those treated with the standard of care (with or without placebo or standard plasma infusions) [RR = 0.92, 95% CI (0.85, 0.99)] based on reported outcomes from RCTs carried out in Europe. Finally, convalescent plasma treatment was not associated with improved survival or clinical outcomes in the 14-day subgroup analyses. Conclusions: Outpatients with COVID-19 treated with convalescent plasma had a statistically significantly lower risk of requiring hospital care when compared to those treated with placebo or the standard of care. However, convalescent plasma treatment was not statistically associated with prolonged survival or improved clinical outcomes when compared to placebo or the standard of care, per overall analysis in hospitalized populations. This hints at potential benefits, when used early, to prevent progression to severe disease. Finally, convalescent plasma was significantly associated with better ICU-related outcomes in trials carried out in Europe. Well-designed prospective studies could clarify its potential benefit for specific subpopulations in the post-pandemic era.

Project 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.

Project description:The objective of this study was to assess whether convalescent plasma therapy could offer survival advantages for patients with novel coronavirus disease 2019 (COVID-19). An electronic search of Pubmed, Web of Science, Embase, Cochrane library and MedRxiv was performed from January 1st, 2020 to April 1st, 2022. We included studies containing patients with COVID-19 and treated with CCP. Data were independently extracted by two reviewers and synthesized with a random-effect analysis model. The primary outcome was 28-d mortality. Secondary outcomes included length of hospital stay, ventilation-free days, 14-d mortality, improvements of symptoms, progression of diseases and requirements of mechanical ventilation. Safety outcomes included the incidence of all adverse events (AEs) and serious adverse events (SAEs). The Cochrane risk-of-bias assessment tool 2.0 was used to assess the potential risk of bias in eligible studies. The heterogeneity of results was assessed by I^2 test and Q statistic test. The possibility of publication bias was assessed by conducting Begg and Egger test. GRADE (Grading of Recommendations Assessment, Development and Evaluation) method were used for quality of evidence. This study had been registered on PROSPERO, CRD42021273608. 32 RCTs comprising 21478 patients with Covid-19 were included. Compared to the control group, COVID-19 patients receiving CCP were not associated with significantly reduced 28-d mortality (CCP 20.0% vs control 20.8%; risk ratio 0.94; 95% CI 0.87-1.02; p = 0.16; I² = 8%). For all secondary outcomes, there were no significant differences between CCP group and control group. The incidence of AEs (26.9% vs 19.4%,; risk ratio 1.14; 95% CI 0.99-01.31; p = 0.06; I² = 38%) and SAEs (16.3% vs 13.5%; risk ratio 1.03; 95% CI 0.87-1.20; p = 0.76; I² = 42%) tended to be higher in the CCP group compared to the control group, while the differences did not reach statistical significance. In all, CCP therapy was not related to significantly improved 28-d mortality or symptoms recovery, and should not be viewed as a routine treatment for COVID-19 patients.Trial registration numberCRD42021273608. Registration on February 28, 2022.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, Identifier CRD42022313265.

Dataset Information

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

Background

Methods

Results

Conclusions

Publications

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

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