Convalescent Plasma for COVID-19: A multicenter, randomized clinical trial

Cristina Avendano-Sola, Antonio Ramos-Martinez, Elena Munez-Rubio, Belen Ruiz-Antoran, Rosa Malo de Molina, Ferran Torres, Ana Fernandez-Cruz, Alejandro Callejas-Diaz, Jorge Calderon, Concepcion Payares-Herrera, Isabel Salcedo, Irene Romera, Jaime Lora-Tamayo, Mikel Mancheno-Losa, Maria Liz Paciello, Carolina Villegas, Vicente Estrada, Isabel Saez-Serrano, Maria Lourdes Porras-Leal, Maria del Castillo Jarilla-Fernandez, Jose Ramon Pano-Pardo, Jose Antonio Moreno-Chulilla, Itziar Arrieta-Aldea, Alba Bosch, Moncef Belhassen-Garcia, Olga Lopez-Villar, Ascension Ramos-Garrido, Lydia Blanco, Maria Elena Madrigal, Enric Contreras, Eduard Muniz-Diaz, Jose Maria Domingo-Morera, Inmaculada Casas-Flecha, Mayte Perez-Olmeda, Javier Garcia-Perez, Jose Alcami, Jose Luis Bueno, Rafael F Duarte doi: https://doi.org/10.1101/2020.08.26.20182444

This article is a preprint and has not been certified by peer review [what does this mean?].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/10.1101/2020.08.26.20182444v2.full.pdf

Abstract

Background: Passive immunotherapy with convalescent plasma (CP) is a potential treatment for COVID-19 for which evidence from controlled clinical trials is lacking. Methods: We conducted a multi-center, randomized clinical trial in patients hospitalized for COVID-19. All patients received standard of care treatment, including off-label use of marketed medicines, and were randomized 1:1 to receive one dose (250-300 mL) of CP from donors with IgG anti-SARS-CoV-2. The primary endpoint was the proportion of patients in categories 5, 6 or 7 of the COVID-19 ordinal scale at day 15. Results: The trial was stopped after first interim analysis due to the fall in recruitment related to pandemic control. With 81 patients randomized, there were no patients progressing to mechanical ventilation or death among the 38 patients assigned to receive plasma (0%) versus 6 out of 43 patients (14%) progressing in control arm. Mortality rates were 0% vs 9.3% at days 15 and 29 for the active and control groups, respectively. No significant differences were found in secondary endpoints. At inclusion, patients had a median time of 8 days (IQR, 6-9) of symptoms and 49,4% of them were positive for anti-SARS-CoV-2 IgG antibodies. Conclusions: Convalescent plasma could be superior to standard of care in avoiding progression to mechanical ventilation or death in hospitalized patients with COVID-19. The strong dependence of results on a limited number of events in the control group prevents drawing firm conclusions about CP efficacy from this trial. (Funded by Instituto de Salud Carlos III; NCT04345523).

Competing Interest Statement

The authors have declared no competing interest.

Clinical Trial

NCT04345523

Funding Statement

This research is funded by the Government of Spain, Ministry of Science and Innovation, Instituto de Salud Carlos III, grant number COV20/00072 (Royal Decree-Law 8/2020, of 17 March, on urgent extraordinary measures to deal with the economic and social impact of COVID-19), co-financed by the European Regional Development Fund (FEDER) A way to make Europe.

https://www.medrxiv.org/content/10.1101/2020.08.26.20182444v2