Current best evidence for clinical care (more info)
Importance: Convalescent plasma is a potential therapeutic option for patients with coronavirus disease 2019 (COVID-19), but further data from randomized clinical trials are needed.
Objective: To evaluate the efficacy and adverse effects of convalescent plasma therapy for patients with COVID-19.
Design, Setting, and Participants: Open-label, multicenter, randomized clinical trial performed in 7 medical centers in Wuhan, China, from February 14, 2020, to April 1, 2020, with final follow-up April 28, 2020. The trial included 103 participants with laboratory-confirmed COVID-19 that was severe (respiratory distress and/or hypoxemia) or life-threatening (shock, organ failure, or requiring mechanical ventilation). The trial was terminated early after 103 of a planned 200 patients were enrolled.
Intervention: Convalescent plasma in addition to standard treatment (n = 52) vs standard treatment alone (control) (n = 51), stratified by disease severity.
Main Outcomes and Measures: Primary outcome was time to clinical improvement within 28 days, defined as patient discharged alive or reduction of 2 points on a 6-point disease severity scale (ranging from 1 [discharge] to 6 [death]). Secondary outcomes included 28-day mortality, time to discharge, and the rate of viral polymerase chain reaction (PCR) results turned from positive at baseline to negative at up to 72 hours.
Results: Of 103 patients who were randomized (median age, 70 years; 60 [58.3%] male), 101 (98.1%) completed the trial. Clinical improvement occurred within 28 days in 51.9% (27/52) of the convalescent plasma group vs 43.1% (22/51) in the control group (difference, 8.8% [95% CI, -10.4% to 28.0%]; hazard ratio [HR], 1.40 [95% CI, 0.79-2.49]; P = .26). Among those with severe disease, the primary outcome occurred in 91.3% (21/23) of the convalescent plasma group vs 68.2% (15/22) of the control group (HR, 2.15 [95% CI, 1.07-4.32]; P = .03); among those with life-threatening disease the primary outcome occurred in 20.7% (6/29) of the convalescent plasma group vs 24.1% (7/29) of the control group (HR, 0.88 [95% CI, 0.30-2.63]; P = .83) (P for interaction = .17). There was no significant difference in 28-day mortality (15.7% vs 24.0%; OR, 0.59 [95% CI, 0.22-1.59]; P = .30) or time from randomization to discharge (51.0% vs 36.0% discharged by day 28; HR, 1.61 [95% CI, 0.88-2.95]; P = .12). Convalescent plasma treatment was associated with a negative conversion rate of viral PCR at 72 hours in 87.2% of the convalescent plasma group vs 37.5% of the control group (OR, 11.39 [95% CI, 3.91-33.18]; P < .001). Two patients in the convalescent plasma group experienced adverse events within hours after transfusion that improved with supportive care.
Conclusion and Relevance: Among patients with severe or life-threatening COVID-19, convalescent plasma therapy added to standard treatment, compared with standard treatment alone, did not result in a statistically significant improvement in time to clinical improvement within 28 days. Interpretation is limited by early termination of the trial, which may have been underpowered to detect a clinically important difference.
Trial Registration: Chinese Clinical Trial Registry: ChiCTR2000029757.
|Discipline / Specialty Area||Score|
|Family Medicine (FM)/General Practice (GP)||
|General Internal Medicine-Primary Care(US)||
The trial was terminated too soon.
I think this trial needs to be considered in the context of our evolving understanding of COVID-19 as a disease with distinct phases of viral proliferation, sometimes followed by a severe inflammatory/prothrombotic state. Convalescent plasma would be expected to be most beneficial in the initial phase when people are not yet severely ill. In most cases, the severely ill patients with COVID-19 have already developed advanced inflammatory and thrombotic issues that seem to be independent of ongoing viral load. I look forward to more reports of early use of convalescent plasma +/- other anti-viral treatments in the earliest phases of symptomatic illness.
The study was under-powered and terminated early. An important conclusion is that the administration of convalescent plasma did not improve recovery time.
This is a good article; the subject of this article already made the mainstream media news.
The study was underpowered; there was a positive trend.
The study found disappointing results of a very promising plasma therapy in severe COVID-19 patients. However the results have some limiting factors such as the small sample size and the open label study design. We still hope to have positive results in future ongoing similar studies at other centres.
This study showed that convalescent plasma led to a statistically significant change in time to clinical improvement in those with severe disease and conversion to a negative viral PCR. There was no change in most clinical endpoints and no difference in mortality, possibly because the trial was stopped early.