Ozanimod Therapy in Patients With COVID-19 Requiring Oxygen Support: A Randomized, Open-Label, Pilot Trial.
COVID-19
bradycardia
immunomodulators
new therapeutic class
pneumonia
sphingosine-1-phosphate receptor ligands
Journal
Chest
ISSN: 1931-3543
Titre abrégé: Chest
Pays: United States
ID NLM: 0231335
Informations de publication
Date de publication:
28 Oct 2023
28 Oct 2023
Historique:
received:
04
05
2023
revised:
26
09
2023
accepted:
20
10
2023
pubmed:
29
10
2023
medline:
29
10
2023
entrez:
28
10
2023
Statut:
aheadofprint
Résumé
Sphingosine-1-phosphate receptor ligands (SRLs) dampen immunopathologic damages in models of viral pneumonia. Is it feasible to administer an SRL therapy, here ozanimod (OZA), to acutely ill patients infected with SARS-CoV-2? The 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 (SOC) or to SOC 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. Twenty-three patients were randomized to the SOC arm, and 20 were randomized to the OZA arm from September 2020 to February 2022. Evaluation of efficacy showed nonsignificant reductions of median duration of respiratory support (6 [range, 3-10] vs 9 [range, 4-12] days; P = .34), median duration of hospitalization (9 [range, 6-12] vs 10 [range, 6-18] days; P = .20), and median time to clinical improvement (4 [range, 3-7] vs 7 [range, 3-11] days; P = .12) for OZA compared with SOC, respectively. Heart rate was significantly lower with OZA (65 [range, 63-67] vs 71 [range, 69-72] beats/min; P < .0001). However, QT and PR intervals were not affected. No severe adverse drug reaction was reported. To our knowledge, SRL utility in severe pneumonia has never been tested in patients. We show for the first time that this new pharmacologic agent can safely be administered to patients hospitalized for viral pneumonia, with potential clinical benefits. Bradycardia was frequent but well tolerated. ClinicalTrials.gov; No.: NCT04405102; URL: www. gov.
Sections du résumé
BACKGROUND
BACKGROUND
Sphingosine-1-phosphate receptor ligands (SRLs) dampen immunopathologic damages in models of viral pneumonia.
RESEARCH QUESTION
OBJECTIVE
Is it feasible to administer an SRL therapy, here ozanimod (OZA), to acutely ill patients infected with SARS-CoV-2?
STUDY DESIGN AND METHODS
METHODS
The 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 (SOC) or to SOC 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.
RESULTS
RESULTS
Twenty-three patients were randomized to the SOC arm, and 20 were randomized to the OZA arm from September 2020 to February 2022. Evaluation of efficacy showed nonsignificant reductions of median duration of respiratory support (6 [range, 3-10] vs 9 [range, 4-12] days; P = .34), median duration of hospitalization (9 [range, 6-12] vs 10 [range, 6-18] days; P = .20), and median time to clinical improvement (4 [range, 3-7] vs 7 [range, 3-11] days; P = .12) for OZA compared with SOC, respectively. Heart rate was significantly lower with OZA (65 [range, 63-67] vs 71 [range, 69-72] beats/min; P < .0001). However, QT and PR intervals were not affected. No severe adverse drug reaction was reported.
INTERPRETATION
CONCLUSIONS
To our knowledge, SRL utility in severe pneumonia has never been tested in patients. We show for the first time that this new pharmacologic agent can safely be administered to patients hospitalized for viral pneumonia, with potential clinical benefits. Bradycardia was frequent but well tolerated.
CLINICAL TRIAL REGISTRATION
BACKGROUND
ClinicalTrials.gov; No.: NCT04405102; URL: www.
CLINICALTRIALS
RESULTS
gov.
Identifiants
pubmed: 37898184
pii: S0012-3692(23)05668-4
doi: 10.1016/j.chest.2023.10.023
pii:
doi:
Banques de données
ClinicalTrials.gov
['NCT04405102']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: F. L. is a shareholder and administrator of the board of directors of OxyNov for the FreeO(2) device used in a few participants in this study. F. M. has financial participation in this company. None declared (P. B.-L., J.-F. S., P. R., T. N., N. C., D. M.).