High-titre methylene blue-treated convalescent plasma as an early treatment for outpatients with COVID-19 a randomised, placebo-controlled trial
Por:
Alemany, A, Millat-Martinez, P, Corbacho-Monne, M, Malchair, P, Ouchi, D, Ruiz-Comellas, A, Ramirez-Morros, A, Codina, JR, Simon, RA, Videla, S, Costes, G, Capdevila-Jauregui, M, Torrano-Soler, P, San Jose, A, Papell, GB, Puig, J, Otero, A, Suarez, JCR, Pellejero, AZ, Roca, FL, Cortez, OR, Garcia, VG, Vidal-Alaball, J, Millan, A, Contreras, E, Grifols, JR, Ancochea, A, Galvan-Femenia, I, Ferreira, FP, Bonet, M, Cantoni, J, Prat, N, Ara, J, Arcarons, AF, Farre, M, Pradenas, E, Blanco, J, Rodriguez-Arias, MA, Rivas, GF, Marks, M, Bassat, Q, Blanco, I, Baro, B, Clotet, B, Mitja, O
Publicada:
1 mar 2022
Ahead of Print:
1 mar 2022
Resumen:
Background Convalescent plasma has been proposed as an early treatment to interrupt the progression of early COVID-19 to severe disease, but there is little definitive evidence. We aimed to assess whether early treatment with convalescent plasma reduces the risk of hospitalisation and reduces SARS-CoV-2 viral load among outpatients with COVID-19.
Methods We did a multicentre, double-blind, randomised, placebo-controlled trial in four health-care centres in Catalonia, Spain. Adult outpatients aged 50 years or older with the onset of mild COVID-19 symptoms 7 days or less before randomisation were eligible for enrolment. Participants were randomly assigned (1:1) to receive one intravenous infusion of either 250-300 mL of ABO-compatible high anti-SARS-CoV-2 IgG titres (EUROIMMUN ratio >= 6) methylene blue-treated convalescent plasma (experimental group) or 250 mL of sterile 0.9% saline solution (control). Randomisation was done with the use of a central web-based system with concealment of the trial group assignment and no stratification. To preserve masking, we used opaque tubular bags that covered the investigational product and the infusion catheter. The coprimary endpoints were the incidence of hospitalisation within 28 days from baseline and the mean change in viral load (in log10 copies per mL) in nasopharyngeal swabs from baseline to day 7. The trial was stopped early following a data safety monitoring board recommendation because more than 85% of the target population had received a COVID-19 vaccine. Primary efficacy analyses were done in the intention-to-treat population, safety was assessed in all patients who received the investigational product. This study is registered with ClinicalTrials.gov, NCT04621123.
Findings Between Nov 10, 2020, and July 28, 2021, we assessed 909 patients with confirmed COVID-19 for inclusion in the trial, 376 of whom were eligible and were randomly assigned to treatment (convalescent plasma n=188 [serum antibody-negative n=160]; placebo n=188 [serum antibody-negative n=166]). Median age was 56 years (IQR 52-62) and the mean symptom duration was 4.4 days (SD 1.4) before random assignment. In the intention-to-treat population, hospitalisation within 28 days from baseline occurred in 22 (12%) participants who received convalescent plasma versus 21 (11%) who received placebo (relative risk 1.05 [95% CI 0.78 to 1.41]). The mean change in viral load from baseline to day 7 was -2.41 log10 copies per mL (SD 1.32) with convalescent plasma and -2.32 log10 copies per mL (1.43) with placebo (crude difference -0.10 log10 copies per mL [95% CI -0.35 to 0.15]). One participant with mild COVID-19 developed a thromboembolic event 7 days after convalescent plasma infusion, which was reported as a serious adverse event possibly related to COVID-19 or to the experimental intervention.
Interpretation Methylene blue-treated convalescent plasma did not prevent progression from mild to severe illness and did not reduce viral load in outpatients with COVID-19. Therefore, formal recommendations to support the use of convalescent plasma in outpatients with COVID-19 cannot be concluded. Funding Grifols, Crowdfunding campaign YoMeCorono. Copyright (C) 2022 Published by Elsevier Ltd. All rights reserved.
Filiaciones:
Alemany, A:
Fight AIDS & Infect Dis Fdn, Badalona 08916, Catalonia, Spain
Hosp Badalona Germans Trias & Pujol, Infect Dis Dept, Badalona, Spain
Univ Barcelona, Fac Med, Barcelona, Spain
Millat-Martinez, P:
Univ Barcelona, ISGlobal, Hosp Clin, Barcelona, Spain
Corbacho-Monne, M:
Fight AIDS & Infect Dis Fdn, Badalona 08916, Catalonia, Spain
Hosp Badalona Germans Trias & Pujol, Infect Dis Dept, Badalona, Spain
Univ Barcelona, Fac Med, Barcelona, Spain
Hosp Univ Parc Tauli, I3PT, Sabadell, Spain
Malchair, P:
Bellvitge Univ Hosp, Emergency Dept, Lhospitalet De Llobregat, Spain
Ouchi, D:
Fight AIDS & Infect Dis Fdn, Badalona 08916, Catalonia, Spain
Univ Autonoma Barcelona, Barcelona, Spain
Ruiz-Comellas, A:
Fundacio Inst Univ Recerca Atencio Primaria Salut, Unitat Suport Recerca Catalunya Cent, St Fruit De Sages, Spain
Inst Catala Salut, Gerencia Terr Catalunya Cent, Hlth Promot Rural Areas Res Grp, St Fruit De Sages, Spain
Univ Vic, Univ Cent Catalunya, Vic, Spain
Ramirez-Morros, A:
Fundacio Inst Univ Recerca Atencio Primaria Salut, Unitat Suport Recerca Catalunya Cent, St Fruit De Sages, Spain
Codina, JR:
Hosp Berga, Salut Catalunya Cent, Berga, Spain
Simon, RA:
Hosp Berga, Salut Catalunya Cent, Berga, Spain
Videla, S:
Bellvitge Univ Hosp, HUB IDIBELL, Clin Res Support Unit, Barcelona, Spain
Bellvitge Univ Hosp, Bellvitge Biomed Res Inst, Barcelona, Spain
Univ Barcelona, IDIBELL, Sch Med & Hlth Sci, Pharmacol Unit,Dept Pathol & Expt Therapeut, Barcelona, Spain
Costes, G:
Fight AIDS & Infect Dis Fdn, Badalona 08916, Catalonia, Spain
Capdevila-Jauregui, M:
Fight AIDS & Infect Dis Fdn, Badalona 08916, Catalonia, Spain
Torrano-Soler, P:
Fight AIDS & Infect Dis Fdn, Badalona 08916, Catalonia, Spain
San Jose, A:
Fight AIDS & Infect Dis Fdn, Badalona 08916, Catalonia, Spain
Papell, GB:
Hosp Badalona Germans Trias & Pujol, Infect Dis Dept, Badalona, Spain
Puig, J:
Fight AIDS & Infect Dis Fdn, Badalona 08916, Catalonia, Spain
Otero, A:
Bellvitge Univ Hosp, Emergency Dept, Lhospitalet De Llobregat, Spain
Bellvitge Univ Hosp, HUB IDIBELL, Clin Res Support Unit, Barcelona, Spain
Bellvitge Univ Hosp, Bellvitge Biomed Res Inst, Barcelona, Spain
Suarez, JCR:
Bellvitge Univ Hosp, Emergency Dept, Lhospitalet De Llobregat, Spain
Pellejero, AZ:
Bellvitge Univ Hosp, Emergency Dept, Lhospitalet De Llobregat, Spain
Roca, FL:
Bellvitge Univ Hosp, Emergency Dept, Lhospitalet De Llobregat, Spain
Cortez, OR:
Bellvitge Univ Hosp, Emergency Dept, Lhospitalet De Llobregat, Spain
Garcia, VG:
Bellvitge Univ Hosp, Emergency Dept, Lhospitalet De Llobregat, Spain
Vidal-Alaball, J:
Fundacio Inst Univ Recerca Atencio Primaria Salut, Unitat Suport Recerca Catalunya Cent, St Fruit De Sages, Spain
Inst Catala Salut, Gerencia Terr Catalunya Cent, Hlth Promot Rural Areas Res Grp, St Fruit De Sages, Spain
Univ Vic, Univ Cent Catalunya, Vic, Spain
Millan, A:
Banc Sang & Teixits, Blood Bank Dept, Barcelona, Spain
Contreras, E:
Banc Sang & Teixits, Blood Bank Dept, Barcelona, Spain
Grifols, JR:
Fight AIDS & Infect Dis Fdn, Badalona 08916, Catalonia, Spain
Banc Sang & Teixits, Blood Bank Dept, Barcelona, Spain
Ancochea, A:
Fight AIDS & Infect Dis Fdn, Badalona 08916, Catalonia, Spain
Banc Sang & Teixits, Blood Bank Dept, Barcelona, Spain
Galvan-Femenia, I:
Fight AIDS & Infect Dis Fdn, Badalona 08916, Catalonia, Spain
Barcelona Inst Sci & Technol, Inst Res Biomed, Barcelona, Spain
Ferreira, FP:
Bioclever, Barcelona, Spain
Bonet, M:
Bioclever, Barcelona, Spain
Cantoni, J:
Bioclever, Barcelona, Spain
Prat, N:
Inst Catala Salut, Gerencia Terr Metropolitana Nord, Barcelona, Spain
Ara, J:
Inst Catala Salut, Gerencia Terr Metropolitana Nord, Barcelona, Spain
Arcarons, AF:
Inst Catala Salut, Gerencia Terr Catalunya Cent, Barcelona, Spain
Farre, M:
Hosp Badalona Germans Trias & Pujol, Infect Dis Dept, Badalona, Spain
Univ Autonoma Barcelona, Barcelona, Spain
Pradenas, E:
Germans Trigs & Pujol Res Inst, IrsiCaixa AIDS Res Inst, Can Ruti Campus, Badalona, Spain
Blanco, J:
Univ Vic, Univ Cent Catalunya, Vic, Spain
Germans Trigs & Pujol Res Inst, IrsiCaixa AIDS Res Inst, Can Ruti Campus, Badalona, Spain
Rodriguez-Arias, MA:
Fight AIDS & Infect Dis Fdn, Badalona 08916, Catalonia, Spain
Rivas, GF:
Clin Lab Metropolitana Nord, Microbiol Dept, Barcelona, Spain
Marks, M:
Hosp Trop Dis, London, England
London Sch Hyg & Trop Med, Clin Res Dept, London, England
Bassat, Q:
Univ Barcelona, ISGlobal, Hosp Clin, Barcelona, Spain
Consorcio Invest Biomed Red Epidemiol & Salud Pub, Madrid, Spain
ICREA, Pg Lluls Co 23, Barcelona, Spain
Univ Barcelona, Pediat Dept, Hosp St Joan De Deu, Barcelona, Spain
Ctr Invest Saude Manhica, Maputo, Mozambique
Blanco, I:
Clin Lab Metropolitana Nord, Management Dept, Barcelona, Spain
Baro, B:
Univ Barcelona, ISGlobal, Hosp Clin, Barcelona, Spain
Clotet, B:
Hosp Badalona Germans Trias & Pujol, Infect Dis Dept, Badalona, Spain
Univ Autonoma Barcelona, Barcelona, Spain
Univ Vic, Univ Cent Catalunya, Vic, Spain
Germans Trigs & Pujol Res Inst, IrsiCaixa AIDS Res Inst, Can Ruti Campus, Badalona, Spain
Mitja, O:
Fight AIDS & Infect Dis Fdn, Badalona 08916, Catalonia, Spain
Hosp Badalona Germans Trias & Pujol, Infect Dis Dept, Badalona, Spain
Univ Vic, Univ Cent Catalunya, Vic, Spain
Int SOS, Lihir Med Ctr, Lihir Isl, Papua N Guinea
Bronze, Green Submitted, Green Published
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