Early Anti-SARS-CoV-2 Convalescent Plasma in COVID: Randomized Phase 2 Trial

View ORCID ProfileMaría Elvira Balcells, View ORCID ProfileLuis Rojas, View ORCID ProfileNicole Le Corre, View ORCID ProfileConstanza Martínez-Valdebenito, View ORCID ProfileMaría Elena Ceballos, Marcela Ferrés, Mayling Chang, Cecilia Vizcaya, Sebastián Mondaca, Álvaro Huete, View ORCID ProfileRicardo Castro, View ORCID ProfileMauricio Sarmiento, Luis Villarroel, Alejandra Pizarro, View ORCID ProfilePatricio Ross, View ORCID ProfileJaime Santander, Bárbara Lara, Marcela Ferrada, Sergio Vargas-Salas, Carolina Beltrán-Pavez, View ORCID ProfileRicardo Soto-Rifo, View ORCID ProfileFernando Valiente-Echeverría, Christian Caglevic, Mauricio Mahave, Carolina Selman, Raimundo Gazitúa, José Luis Briones, Franz Villarroel-Espindola, View ORCID ProfileCarlos Balmaceda, View ORCID ProfileManuel A. Espinoza, Jaime Pereira, Bruno Nervi

doi: https://doi.org/10.1101/2020.09.17.20196212

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2020.09.17.20196212v1.full.pdf

Abstract

Background: Convalescent plasma (CP), despite limited evidence on its efficacy, is being widely used as a compassionate therapy for hospitalized patients with COVID-19. We aimed to evaluate the efficacy and safety of early CP therapy in COVID-19 progression. Methods: Open-label, single-center, randomized clinical trial performed in an academic center in Santiago, Chile from May 10, 2020, to July 18, 2020, with final follow-up August 17, 2020. The trial included patients hospitalized within the first 7 days of COVID-19 symptoms onset, presenting risk factors for illness progression and not on mechanical ventilation. The intervention consisted in immediate CP (early plasma group) versus no CP unless developing pre-specified criteria of deterioration (deferred plasma group). Additional standard treatment was allowed in both arms. The primary outcome was a composite of mechanical ventilation, hospitalization for >14 days or death. Key secondary outcomes included: time to respiratory failure, days of mechanical ventilation, hospital length-of-stay, mortality at 30 days, and SARS-CoV-2 RT-PCR clearance rate. Results: Of 58 randomized patients (mean age, 65.8 years, 50% male), 57 (98.3%) completed the trial. A total of 13 (43.3%) participants from the deferred group received plasma based on clinical aggravation. We found no benefit in the primary outcome (32.1% vs 33.3%, OR 0.95, 95% CI 0.32-2.84, p>0.99) in the early versus deferred CP group. In-hospital mortality rate was 17.9% vs 6.7% (OR 3.04, 95% CI 0.54-17.2, p=0.25), mechanical ventilation 17.9% vs 6.7% (OR 3.04, 95% CI 0.54-17.2, p=0.25), and prolonged hospitalization 21.4% vs 30% (OR 0.64, 95%CI, 0.19-2.1, p=0.55) in early versus deferred CP group, respectively. Viral clearance rate on day 3 (26% vs 8%, p=0.20) and day 7 (38% vs 19%, p=0.37) did not differ between groups. Two patients experienced serious adverse events within 6 or less hours after plasma transfusion. Conclusion: Immediate addition of CP therapy in early stages of COVID-19 -compared to its use only in case of patient deterioration- did not confer benefits in mortality, length of hospitalization or mechanical ventilation requirement.

Competing Interest Statement

The authors have declared no competing interest.

Clinical Trial

NCT04375098

Funding Statement

This work was supported by a grant from Fondo de Adopción Tecnológica SiEmpre, SOFOFA Hub, and Ministerio de Ciencia, Tecnología Conocimiento e Innovación Chile.

https://www.medrxiv.org/content/10.1101/2020.09.17.20196212v1