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

J Clin Invest. 2021 Oct 15;131(20):e152740. doi: 10.1172/JCI152740.

Abstract

BACKGROUNDPassive immunotherapy with convalescent plasma (CP) is a potential treatment for COVID-19. Evidence from controlled clinical trials is inconclusive.METHODSWe 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.RESULTSBetween 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).CONCLUSIONCP 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 REGISTRATIONClinicaltrials.gov, NCT04345523.FUNDINGGovernment of Spain, Instituto de Salud Carlos III.

Keywords: COVID-19; Immunotherapy.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • COVID-19 / mortality
  • COVID-19 / physiopathology
  • COVID-19 / therapy*
  • COVID-19 Serotherapy
  • Combined Modality Therapy
  • Disease Progression
  • Female
  • Hospitalization
  • Humans
  • Immunization, Passive / adverse effects
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Odds Ratio
  • Pandemics
  • SARS-CoV-2*
  • Spain / epidemiology
  • Treatment Outcome

Associated data

  • ClinicalTrials.gov/NCT04345523