tetano
Editor, Senior Moderator
Cardiol J
. 2022 Aug 1.
doi: 10.5603/CJ.a2022.0072. Online ahead of print.
Ion channel inhibition with amiodarone or verapamil in symptomatic hospitalized nonintensive-care COVID-19 patients: The ReCOVery-SIRIO randomized trial
Eliano P Navarese[SUP] 1 2 3 [/SUP], Przemysław Podhajski[SUP] 4 [/SUP], Felicita Andreotti[SUP] 5 6 [/SUP], Giuseppe La Torre[SUP] 7 [/SUP], Robert Gajda[SUP] 8 [/SUP], Adrian Radziwanowski[SUP] 4 [/SUP], Małgorzata Nowicka[SUP] 4 [/SUP], Paweł Bukowski[SUP] 8 [/SUP], Jacek Gajda[SUP] 8 [/SUP], Maciej Omyła[SUP] 8 [/SUP], Piotr Lackowski[SUP] 4 [/SUP], Maciej Piasecki[SUP] 4 [/SUP], Małgorzata Jasiewicz[SUP] 4 [/SUP], Paweł Szymański[SUP] 9 [/SUP], Łukasz Pietrzykowski[SUP] 4 [/SUP], Piotr Michalski[SUP] 4 [/SUP], Aldona Kubica[SUP] 10 [/SUP], Iwona Urbanowicz[SUP] 4 [/SUP], Nicola Orsini[SUP] 11 [/SUP], Max Conte[SUP] 12 [/SUP], Jarosław Pinkas[SUP] 13 [/SUP], Marc A Brouwer[SUP] 14 [/SUP], Jacek Kubica[SUP] 4 [/SUP]
Affiliations
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 Recovery-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
, 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: COVID-19; amiodarone; ion-channel inhibition; randomized trial; verapamil.
. 2022 Aug 1.
doi: 10.5603/CJ.a2022.0072. Online ahead of print.
Ion channel inhibition with amiodarone or verapamil in symptomatic hospitalized nonintensive-care COVID-19 patients: The ReCOVery-SIRIO randomized trial
Eliano P Navarese[SUP] 1 2 3 [/SUP], Przemysław Podhajski[SUP] 4 [/SUP], Felicita Andreotti[SUP] 5 6 [/SUP], Giuseppe La Torre[SUP] 7 [/SUP], Robert Gajda[SUP] 8 [/SUP], Adrian Radziwanowski[SUP] 4 [/SUP], Małgorzata Nowicka[SUP] 4 [/SUP], Paweł Bukowski[SUP] 8 [/SUP], Jacek Gajda[SUP] 8 [/SUP], Maciej Omyła[SUP] 8 [/SUP], Piotr Lackowski[SUP] 4 [/SUP], Maciej Piasecki[SUP] 4 [/SUP], Małgorzata Jasiewicz[SUP] 4 [/SUP], Paweł Szymański[SUP] 9 [/SUP], Łukasz Pietrzykowski[SUP] 4 [/SUP], Piotr Michalski[SUP] 4 [/SUP], Aldona Kubica[SUP] 10 [/SUP], Iwona Urbanowicz[SUP] 4 [/SUP], Nicola Orsini[SUP] 11 [/SUP], Max Conte[SUP] 12 [/SUP], Jarosław Pinkas[SUP] 13 [/SUP], Marc A Brouwer[SUP] 14 [/SUP], Jacek Kubica[SUP] 4 [/SUP]
Affiliations
- PMID: 35912711
- DOI: 10.5603/CJ.a2022.0072
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 Recovery-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
, 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: COVID-19; amiodarone; ion-channel inhibition; randomized trial; verapamil.