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Ion channel inhibition with amiodarone or verapamil in symptomatic hospitalized nonintensive-care COVID-19 patients: The ReCOVery-SIRIO randomized trial
Affiliations- Faculty of Medicine, University of Alberta, Edmonton, Canada
- SIRIO MEDICINE research network, Poland
- Interventional Cardiology and Cardiovascular Medicine Research, Department of Cardiology and Internal Medicine, Nicolaus Copernicus University, Bydgoszcz, Poland
- Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
- Catholic University Medical School, Rome, Italy
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
- Department of Infectious Diseases, District Hospital, Pultusk, Poland
- Department of Infectious Diseases, Regional Hospital, Grudziadz, Poland
- Department of Health Promotion, Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Poland
- Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden
- Anesthesia and Intensive Care Unit, Ospedale Bari Sud Di Venere, Bari, Italy
- Center of Postgraduate Medical Education, School of Public Health, Warsaw, Poland
- Department of Cardiology, Radboud University Medical Centre, Nijmegen, the Netherlands
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Abstract
Background: Ion channel inhibition may offer protection against coronavirus disease 2019 (COVID-19). Inflammation and reduced platelet count occur during COVID-19 but precise quantification of risk thresholds is unclear. The Recov ery-SIRIO study aimed to assess clinical effects of amiodarone and verapamil and to relate patient phenotypes to outcomes.
Methods: RECOVERY-SIRIO is a multicenter open-label 1:1:1 investigator-initiated randomized trial with blinded event adjudication. A sample of 804 symptomatic hospitalized nonintensive-care COVID-19 patients, follow-up for 28 days was initially planned.
Results: The trial was stopped when a total of 215 patients had been randomized to amiodarone (n = 71), verapamil (n = 72) or standard care alone (n = 72). At 15 days, the hazard ratio (hazard ratio [HR], 95% confidence interval [CI]) for clinical improvement was 0.77 (0.52–1.14) with amiodarone and 0.97 (0.81–1.17) with verapamil as compared to usual care. Clinically relevant associations were found between mortality or lack of clinical improvement and higher peak C-reactive protein (CRP) levels or nadir platelet count at 7, 10 and 15 days. Mortality rate increased by 73% every 5 mg/dL increment in peak CRP (HR 1.73, 95% CI 1.27–2.37) and was two-fold higher for every decrement of 100 units in nadir platelet count (HR 2.19, 95% CI 1.37–3.51). By cluster analysis, thresholds of 5 mg/dL for peak CRP and 187 × 103/mcL for nadir platelet count identified the phenogroup at greatest risk of dying.
Conclusions: In this randomized trial, neither amiodarone nor verapamil were found to significantly accelerate short-term clinical improvement. Peak CRP and nadir platelet counts were associated with increased mortality both in isolation and by cluster analysis.
Abstract
Background: Ion channel inhibition may offer protection against coronavirus disease 2019 (COVID-19). Inflammation and reduced platelet count occur during COVID-19 but precise quantification of risk thresholds is unclear. The Recov ery-SIRIO study aimed to assess clinical effects of amiodarone and verapamil and to relate patient phenotypes to outcomes.
Methods: RECOVERY-SIRIO is a multicenter open-label 1:1:1 investigator-initiated randomized trial with blinded event adjudication. A sample of 804 symptomatic hospitalized nonintensive-care COVID-19 patients, follow-up for 28 days was initially planned.
Results: The trial was stopped when a total of 215 patients had been randomized to amiodarone (n = 71), verapamil (n = 72) or standard care alone (n = 72). At 15 days, the hazard ratio (hazard ratio [HR], 95% confidence interval [CI]) for clinical improvement was 0.77 (0.52–1.14) with amiodarone and 0.97 (0.81–1.17) with verapamil as compared to usual care. Clinically relevant associations were found between mortality or lack of clinical improvement and higher peak C-reactive protein (CRP) levels or nadir platelet count at 7, 10 and 15 days. Mortality rate increased by 73% every 5 mg/dL increment in peak CRP (HR 1.73, 95% CI 1.27–2.37) and was two-fold higher for every decrement of 100 units in nadir platelet count (HR 2.19, 95% CI 1.37–3.51). By cluster analysis, thresholds of 5 mg/dL for peak CRP and 187 × 103/mcL for nadir platelet count identified the phenogroup at greatest risk of dying.
Conclusions: In this randomized trial, neither amiodarone nor verapamil were found to significantly accelerate short-term clinical improvement. Peak CRP and nadir platelet counts were associated with increased mortality both in isolation and by cluster analysis.
Keywords
amiodarone, verapamil, COVID-19, ion-channel inhibition, randomized trial
About this articleTitle
Ion channel inhibition with amiodarone or verapamil in symptomatic hospitalized nonintensive-care COVID-19 patients: The ReCOVery-SIRIO randomized trial
Journal
Issue
Article type
Original Article
Pages
739-750
Published online
2022-07-29
Page views
4201
Article views/downloads
701
DOI
Pubmed
Bibliographic record
Cardiol J 2022;29(5):739-750.
Keywords
amiodarone
verapamil
COVID-19
ion-channel inhibition
randomized trial
Authors
Eliano P. Navarese
Przemysław Podhajski
Felicita Andreotti
Giuseppe La Torre
Robert Gajda
Adrian Radziwanowski
Małgorzata Nowicka
Paweł Bukowski
Jacek Gajda
Maciej Omyła
Piotr Lackowski
Maciej Piasecki
Małgorzata Jasiewicz
Paweł Szymański
Łukasz Pietrzykowski
Piotr Michalski
Aldona Kubica
Iwona Urbanowicz
Nicola Orsini
Max Conte
Jarosław Pinkas
Marc A. Brouwer
Jacek Kubica
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