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Convalescent plasma for hospitalized patients with COVID-19: an open-label, randomized controlled trial

Our take —

COVID-19 convalescent plasma has been widely employed in the US through an Extended Access Program. However, the results of this randomized clinical trial of 938 hospitalized patients needing oxygen support, which took place between May 2020 and January 2021, show that convalescent plasma does not reduce mortality or the need for intubation at 30 days post enrollment. Furthermore, the risk of serious adverse effects (worsening hypoxemia, respiratory failure) was significantly increased in patients who received convalescent plasma treatment (33.4% vs 26.4%, RR 1.27). The results of this study provide further evidence against the use of convalescent plasma for patients hospitalized with COVID-19.

Study design

Randomized Controlled Trial

Study population and setting

The study described in this article is a multi-center, open-label randomized controlled trial of 938 patients hospitalized within 12 days of onset with COVID-19 needing oxygen support. The study was conducted between May 14, 2020 and January 29, 2021, across 72 hospitals in the US, Canada, and Brazil. The study compared the proportion of patients who died or who required intubation within 30 days of enrollment between those receiving standard of care (n = 307) and those receiving COVID-19 convalescent plasma (n = 614). Secondary analyses of note include that of safety of convalescent plasma, as well as the role of antibodies in modifying the effect of convalescent plasma.

Summary of Main Findings

The trial was stopped at 78% of planned enrollment after an interim analysis suggested no benefit to the intervention group. In an intention-to-treat analysis, 199/614 (32.4%) of patients in the convalescent plasma group died or were intubated within 30 days, versus 86/307 (28.0%) in the standard of care group, a nonsignificant difference (RR 1.16, 95% CI: 0.94 – 1.43, p 0.18). Subgroup analysis found that patients receiving plasma from supplier 3, as well as patients not on corticosteroids, had worse outcomes when receiving convalescent plasma compared to standard of care. However, there were no significant differences in outcomes of any other subgroup analyses, including age, sex, ethnicity, blood type, smoking history, comorbidities, disease timeline, or level of oxygen dependency. Serious adverse events, typically worsening hypoxemia and respiratory failure, were significantly more likely in the convalescent plasma group (33.4%) compared to the standard of care group (26.4%; RR 1.27, 95% CI: 1.02 – 1.57, p 0.034).

Study Strengths

A major strength of this study was the additional serological testing of the plasma, which identifies factors that change and may explain variations in the treatment effect. Specifically, the study found plasma with higher capability for antibody-dependent cell cytotoxicity reduced the odds ratio by 24% per unit (95% CI 0.62 – 0.92). Similarly, plasma with higher capability for neutralization reduced the odds ratio by 23% per unit (95% C1 0.63 – 0.94). Another strength of the study was the accompanying meta-analysis, which summarized evidence both from studies that evaluated exclusively high-titer convalescent plasma therapy and those that evaluated  convalescent plasma of indiscriminate titer but found no evidence of benefit from either approach.

Limitations

This is an open-label study, which can introduce bias into the observation and reporting of adverse effects, as well as the planning of treatment strategies and potentially skew the data.

Value added

This study corroborates previous randomized controlled trials in finding that treatment with COVID-19 convalescent plasma does not reduce mortality or need for intubation at 30 days. In addition, this study found that convalescent plasma treatment was significantly more likely to lead to serious adverse effects, including worsening hypoxemia and respiratory failure, compared to usual standard of care.

This review was posted on: 2 November 2021