• François Lellouche, Pascale Blais-Lecours, François Maltais, Jean-François Sarrazin, Philippe Rola, Tuyen Nguyen, Nathalie Châteauvert, and David Marsolais.
• Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval, Quebec City, QC, Canada; Department of Medicine, Université Laval, Quebec City, QC, Canada. Electronic address: francois.lellouche@criucpq.ulaval.ca.
• Chest. 2024 Apr 1; 165 (4): 810819810-819.

BackgroundSphingosine-1-phosphate receptor ligands (SRLs) dampen immunopathologic damages in models of viral pneumonia.Research QuestionIs it feasible to administer an SRL therapy, here ozanimod (OZA), to acutely ill patients infected with SARS-CoV-2?Study Design And MethodsThe prospective randomized open-label COVID-19 Ozanimod Intervention (COZI) pilot trial was conducted in three Canadian hospitals. Patients admitted for COVID-19 requiring oxygen were eligible. Randomization was stratified for risk factors of poor outcome and oxygen needs at inclusion. Participants were allocated to standard of care or to standard of care plus OZA. OZA (oral, once daily, incremental dosage) was administered for a maximum of 14 days. Primary end point investigated for size effect and variance over time was the assessment of safety and efficacy, evaluated by the daily score on the World Health Organization-adapted six-point ordinal scale for clinical improvement analyzed under the intention-to-treat principle.ResultsTwenty-three patients were randomized to the standard of care arm, and 20 were randomized to the OZA arm from September 2020 to February 2022. Evaluation of efficacy showed nonsignificant reductions of median (interquartile range) duration of respiratory support (6 [3-10] vs 9 [4-12] days; P = .34), median duration of hospitalization (9 [6-12] vs 10 [6-18] days; P = .20), and median time to clinical improvement (4 [3-7] vs 7 [3-11] days; P = .12) for OZA compared with standard of care, respectively. Heart rate was significantly lower with OZA (65 [ 63-67] vs 71 [69-72] beats/min; P < .0001). However, QT and PR intervals were not affected. No severe adverse drug reaction was reported.InterpretationTo our knowledge, SRL utility in severe pneumonia has never been tested in patients. This study shows for the first time that this new pharmacologic agent may safely be administered to patients hospitalized for viral pneumonia, with potential clinical benefits. Bradycardia was frequent but well tolerated.Clinical Trial RegistrationClinicalTrials.gov; No.: NCT04405102; URL: www.Clinicaltrialsgov.Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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