1.
Association of Convalescent Plasma Treatment With Clinical Status in Patients Hospitalized With COVID-19: A Meta-analysis
Troxel AB, Petkova E, Goldfeld K, Liu M, Tarpey T, Wu Y, Wu D, Agarwal A, Avendaño-Solá C, Bainbridge E, et al
JAMA network open. 2022;5(1):e2147331
Abstract
IMPORTANCE COVID-19 convalescent plasma (CCP) is a potentially beneficial treatment for COVID-19 that requires rigorous testing. OBJECTIVE To compile individual patient data from randomized clinical trials of CCP and to monitor the data until completion or until accumulated evidence enables reliable conclusions regarding the clinical outcomes associated with CCP. DATA SOURCES From May to August 2020, a systematic search was performed for trials of CCP in the literature, clinical trial registry sites, and medRxiv. Domain experts at local, national, and international organizations were consulted regularly. STUDY SELECTION Eligible trials enrolled hospitalized patients with confirmed COVID-19, not receiving mechanical ventilation, and randomized them to CCP or control. The administered CCP was required to have measurable antibodies assessed locally. DATA EXTRACTION AND SYNTHESIS A minimal data set was submitted regularly via a secure portal, analyzed using a prespecified bayesian statistical plan, and reviewed frequently by a collective data and safety monitoring board. MAIN OUTCOMES AND MEASURES Prespecified coprimary end points-the World Health Organization (WHO) 11-point ordinal scale analyzed using a proportional odds model and a binary indicator of WHO score of 7 or higher capturing the most severe outcomes including mechanical ventilation through death and analyzed using a logistic model-were assessed clinically at 14 days after randomization. RESULTS Eight international trials collectively enrolled 2369 participants (1138 randomized to control and 1231 randomized to CCP). A total of 2341 participants (median [IQR] age, 60 [50-72] years; 845 women [35.7%]) had primary outcome data as of April 2021. The median (IQR) of the ordinal WHO scale was 3 (3-6); the cumulative OR was 0.94 (95% credible interval [CrI], 0.74-1.19; posterior probability of OR <1 of 71%). A total of 352 patients (15%) had WHO score greater than or equal to 7; the OR was 0.94 (95% CrI, 0.69-1.30; posterior probability of OR <1 of 65%). Adjusted for baseline covariates, the ORs for mortality were 0.88 at day 14 (95% CrI, 0.61-1.26; posterior probability of OR <1 of 77%) and 0.85 at day 28 (95% CrI, 0.62-1.18; posterior probability of OR <1 of 84%). Heterogeneity of treatment effect sizes was observed across an array of baseline characteristics. CONCLUSIONS AND RELEVANCE This meta-analysis found no association of CCP with better clinical outcomes for the typical patient. These findings suggest that real-time individual patient data pooling and meta-analysis during a pandemic are feasible, offering a model for future research and providing a rich data resource.
2.
Prospective individual patient data meta-analysis of two randomized trials on convalescent plasma for COVID-19 outpatients
Millat-Martinez P, Gharbharan A, Alemany A, Rokx C, Geurtsvankessel C, Papageourgiou G, van Geloven N, Jordans C, Groeneveld G, Swaneveld F, et al
Nature communications. 2022;13(1):2583
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Abstract
Data on convalescent plasma (CP) treatment in COVID-19 outpatients are scarce. We aimed to assess whether CP administered during the first week of symptoms reduced the disease progression or risk of hospitalization of outpatients. Two multicenter, double-blind randomized trials (NCT04621123, NCT04589949) were merged with data pooling starting when <20% of recruitment target was achieved. A Bayesian-adaptive individual patient data meta-analysis was implemented. Outpatients aged ≥50 years and symptomatic for ≤7days were included. The intervention consisted of 200-300mL of CP with a predefined minimum level of antibodies. Primary endpoints were a 5-point disease severity scale and a composite of hospitalization or death by 28 days. Amongst the 797 patients included, 390 received CP and 392 placebo; they had a median age of 58 years, 1 comorbidity, 5 days symptoms and 93% had negative IgG antibody-test. Seventy-four patients were hospitalized, 6 required mechanical ventilation and 3 died. The odds ratio (OR) of CP for improved disease severity scale was 0.936 (credible interval (CI) 0.667-1.311); OR for hospitalization or death was 0.919 (CI 0.592-1.416). CP effect on hospital admission or death was largest in patients with ≤5 days of symptoms (OR 0.658, 95%CI 0.394-1.085). CP did not decrease the time to full symptom resolution. TRIAL REGISTRATION Clinicaltrials.gov NCT04621123 and NCT04589949. REGISTRATION NCT04621123 and NCT04589949 on https://www. CLINICALTRIALS gov.
PICO Summary
Population
COVID-19 outpatients enrolled in two multicenter trials: COnV-ert and CoV-Early (n= 797).
Intervention
Convalescent plasma (n= 390).
Comparison
Placebo (n= 392).
Outcome
Seventy-four patients were hospitalized, 6 required mechanical ventilation and 3 died. The odds ratio (OR) of convalescent plasma for improved disease severity scale was 0.936; OR for hospitalization or death was 0.919. The convalescent plasma effect on hospital admission or death was largest in patients with ≤5 days of symptoms (OR 0.658). Convalescent plasma did not decrease the time to full symptom resolution.