A multicenter randomized open-label clinical trial for convalescent plasma in patients hospitalized with COVID-19 pneumonia

Background: Passive immunotherapy with convalescent plasma (CP) is a potential treatment for COVID-19. Evidence from controlled clinical trials is inconclusive. Methods: We conducted a randomized, open-label, controlled clinical trial at 27 hospitals in Spain. Patients had to be admitted for COVID-19 pneumonia within 7 days from symptom onset and not on mechanical ventilation or high-flow oxygen devices. Patients were randomized 1:1 to treatment with CP in addition to standard of care (SOC) or to the control arm receiving only SOC. The primary endpoint was the proportion of patients in categories 5 (noninvasive ventilation or high-flow oxygen), 6 (invasive mechanical ventilation or extracorporeal membrane oxygenation [ECMO]), or 7 (death) at 14 days. Primary analysis was performed in the intention-to-treat population. Results: Between April 4, 2020, and February 5, 2021, 350 patients were randomly assigned to either CP (n = 179) or SOC (n = 171). At 14 days, proportion of patients in categories 5, 6, or 7 was 11.7% in the CP group versus 16.4% in the control group (P = 0.205). The difference was greater at 28 days, with 8.4% of patients in categories 5-7 in the CP group versus 17.0% in the control group (P = 0.021). The difference in overall survival did not reach statistical significance (HR 0.46, 95% CI 0.19-1.14, log-rank P = 0.087). Conlusion: CP showed a significant benefit in preventing progression to noninvasive ventilation or high-flow oxygen, invasive mechanical ventilation or ECMO, or death at 28 days. The effect on the predefined primary endpoint at 14 days and the effect on overall survival were not statistically significant. Trial registration: Clinicaltrials.gov, NCT04345523.This research was funded by the Government of Spain, Ministry of Science and Innovation, Instituto de Salud Carlos III, grant number COV20/00072 (Royal DecreeLaw 8/2020, of 17 March, on urgent extraordinary measures to deal with the economic and social impact of COVID-19), cofinanced by the European Regional Development Fund (FEDER) “A way to make Europe,” and supported by SCReN (Spanish Clinical Research Network), Instituto de Salud Carlos III, project PT17/0017/0009. Clinical trial insurance coverage was donated by MARCH RS Correduría de Seguros y Reaseguros. MML holds a “Río Hortega” research contract (CM19/00226). See Supplemental Material for details on the ConPlas-19 study group.S