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

Cristina Avendaño-Solá, Antonio Ramos-Martínez, Elena Muñez-Rubio, Belen Ruiz-Antorán, Rosa Malo de Molina, Ferran Torres, Ana Fernández-Cruz, Jorge Calderon-Parra, Concepcion Payares-Herrera, Alberto Díaz de Santiago, Irene Romera Martínez, Ilduara Pintos, Jaime Lora-Tamayo, Mikel Mancheño-Losa, Maria Liz Paciello Coronel, A L Martinez-Gonzalez, Julia Vidán-Estévez, Maria José Nuñez-Orantos, Maria Isabel Saez-Serrano, Maria Lourdes Porras-LealMaria Del Castillo Jarilla-Fernández, Paula Villares, Jaime Perez de Oteyza, Ascensión Ramos-Garrido, Lydia Blanco, Maria Elena Madrigal-Sánchez, Martín Rubio-Batllés, Ana Velasco-Iglesias, José Ramón Paño-Pardo, J A Moreno-Chulilla, Eduardo Muñiz-Diaz, Inmaculada Casas-Flecha, Mayte Pérez-Olmeda, Javier García-Pérez, Jose Alcami, José Luis Bueno, Rafael F Duarte

Research output: Contribution to journalArticleResearchpeer-review

59 Citations (Scopus)

Abstract

BACKGROUND: Passive immunotherapy with convalescent plasma (CP) is a potential treatment for COVID-19 for which 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 (non-invasive ventilation or high-flow oxygen), 6 (invasive mechanical ventilation or extracorporeal membrane oxygenation [ECMO]), or 7(death) at 14 days, and 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 on categories 5, 6 or 7 was 11.7% in CP group versus 16.4% in control group (p=0.205). The difference was greater at 28 days, with 8.4% of patients in categories 5-7 in CP group versus 17.0% in 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).

CONCLUSION: CP showed a significant benefit in preventing progression to non-invasive 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, NCT04345523FUNDING. Government of Spain, Instituto de Salud Carlos III.

Original languageEnglish
Article numbere152740
JournalJournal of Clinical Investigation
Volume131
Issue number20
Early online date2 Sept 2021
DOIs
Publication statusPublished - 2 Sept 2021

Keywords

  • Aged
  • COVID-19/mortality
  • 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

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