• Fernando G Zampieri, Glauco Adrieno Westphal, Maria Adelaide Dos Santos, Samara P C Gomes, Jackeline O Gomes, Karina L Negrelli, Renato H N Santos, Luciana M Ishihara, Tamiris A Miranda, Ligia N Laranjeira, Nanci Valeis, Eliana Vieira Santucci, de Souza DantasVicente CésVCHospital Naval Marcílio Dias, Rio de Janeiro, RJ, Brazil., Otávio Gebara, Danny M Cohn, Gustavo Buchele, Mariano Janiszewski, Flávio Geraldo de Freitas, Felipe Dal-Pizzol, de Matos SoeiroAlexandreAInstituto do Coração do Hospital das Clínicas da FMUSP, São Paulo, SP, Brazil., Isabele Ribeiro Berti, Almir Germano, Daniel Almeida Schettini, Regis G Rosa, Maicon Falavigna, Viviane C Veiga, AzevedoLuciano C PLCPHospital Israelita Albert Einstein, São Paulo, SP, Brazil; Universidade Federal de São Paulo, São Paulo, SP, Brazil., Lucas P Damiani, Flávia R Machado, Alexandre B Cavalcanti, and BRICNet.
• HCOR Research Institute, São Paulo, SP, Brazil; Department of Critical Care Medicine, University of Alberta, Edmonton, Canada. Electronic address: fzampier@ualberta.ca.
• J Crit Care. 2024 Dec 1; 84: 154892154892.

PurposeTo assess the effect of antisense therapy to block kallikrein-kinin pathway in COVID-19 patients.Material And MethodsRandomized, placebo-controlled, double blind, controlled trial enrolling hospitalized COVID-19 patients that required supplementary oxygen to sustain peripheral oxygen saturation. Key exclusion criteria included use of mechanical ventilation or vasopressors, and patients with more than 10 days since symptom onset or more than 48 h of oxygen use. Patients were randomized to either one subcutaneous dose of ISIS721744, an antisense that blocks prekallikrein, or placebo. The primary outcome was the number of days alive and free of oxygen support up to 15 days (DAFOR15). Secondary endpoints included organ failure score, need and duration of mechanical ventilation up to 15 days, and all-cause mortality at 30 days. Exploratory endpoints included physiological parameters, biomarkers, and quality of life.ResultsFrom October 10, 2020, to December 09, 2020, 111 patients were randomized at thirteen sites in Brazil (56 to treatment and 55 to control group). Average age was 57.5 years, and most patients were male (68.5%). There were no significant differences in DAFOR15 between groups (5.9 ± 5.2 days for the intervention arm and 7.7 ± 5.1 for the control group; mean difference - 0.65, 95% confidence intervals from -2.95 to 1.36, p = 0.520).ConclusionAntisense therapy designed to block the kallikrein-kinin pathway did not demonstrate clinical benefits in increasing days-alive without respiratory support at 15 days in patients with COVID-19 during the first wave in 2020.Gov IdentifierNCT04549922.Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

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