Effect of High-Titer Convalescent Plasma on Progression to Severe Respiratory Failure or Death in Hospitalized Patients with COVID-19 Pneumonia: A Randomized Clinical Trial

Francesco Menichetti, Patrizia Popoli, Maria Puopolo, Stefania Spila Alegiani, Giusy Tiseo, Alessandro Bartoloni, Giuseppe Vittorio De Socio, Sauro Luchi, Pierluigi Blanc, Massimo Puoti, Elena Toschi, Marco Massari, Lucia Palmisano, Giuseppe Marano, Margherita Chiamenti, Laura Martinelli, Silvia Franchi, Carlo Pallotto, Lorenzo Roberto Suardi, Barbara Luciani PasquaMarco Merli, Plinio Fabiani, Luca Bertolucci, Beatrice Borchi, Sara Modica, Sara Moneta, Giulia Marchetti, Antonella D'Arminio Monforte, Laura Stoppini, Nadia Ferracchiato, Stefania Piconi, Claudio Fabbri, Enrico Beccastrini, Riccardo Saccardi, Andrea Giacometti, Sara Esperti, Piera Pierotti, Laura Bernini, Claudia Bianco, Sara Benedetti, Alessandra Lanzi, Paolo Bonfanti, Marco Massari, Spartaco Sani, Annalisa Saracino, Antonella Castagna, Luigia Trabace, Maria Lanza, Daniele Focosi, Marco Falcone

Research output: Contribution to journalArticlepeer-review

Abstract

Importance: Convalescent plasma (CP) has been generally unsuccessful in preventing worsening of respiratory failure or death in hospitalized patients with COVID-19 pneumonia. Objective: To evaluate the efficacy of CP plus standard therapy (ST) vs ST alone in preventing worsening respiratory failure or death in patients with COVID-19 pneumonia. Design, Setting, and Participants: This prospective, open-label, randomized clinical trial enrolled (1:1 ratio) hospitalized patients with COVID-19 pneumonia to receive CP plus ST or ST alone between July 15 and December 8, 2020, at 27 clinical sites in Italy. Hospitalized adults with COVID-19 pneumonia and a partial pressure of oxygen-to-fraction of inspired oxygen (Pao2/Fio2) ratio between 350 and 200 mm Hg were eligible. Interventions: Patients in the experimental group received intravenous high-titer CP (≥1:160, by microneutralization test) plus ST. The volume of infused CP was 200 mL given from 1 to a maximum of 3 infusions. Patients in the control group received ST, represented by remdesivir, glucocorticoids, and low-molecular weight heparin, according to the Agenzia Italiana del Farmaco recommendations. Main Outcomes and Measures: The primary outcome was a composite of worsening respiratory failure (Pao2/Fio2ratio <150 mm Hg) or death within 30 days from randomization. Results: Of the 487 randomized patients (241 to CP plus ST; 246 to ST alone), 312 (64.1%) were men; the median (IQR) age was 64 (54.0-74.0) years. The modified intention-to-treat population included 473 patients. The primary end point occurred in 59 of 231 patients (25.5%) treated with CP and ST and in 67 of 239 patients (28.0%) who received ST (odds ratio, 0.88; 95% CI, 0.59-1.33; P =.54). Adverse events occurred more frequently in the CP group (12 of 241 [5.0%]) compared with the control group (4 of 246 [1.6%]; P =.04). Conclusions and Relevance: In patients with moderate to severe COVID-19 pneumonia, high-titer anti-SARS-CoV-2 CP did not reduce the progression to severe respiratory failure or death within 30 days. Trial Registration: ClinicalTrials.gov Identifier: NCT04716556.

Original languageEnglish
Article numbere2136246
JournalJAMA network open
DOIs
Publication statusAccepted/In press - 2021

ASJC Scopus subject areas

  • Medicine(all)

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