Amiodarone or Verapamil in COVID-19 Hospitalized Patients With Symptoms (ReCOVery-SIRIO)

There is an urgent need for effective therapies against the novel COVID-19 virus. Studies have shown that amiodarone and verapamil can interfere with coronavirus entry and amplification by blocking ion channels. ReCOVery-SIRIO is a randomized study to investigate amiodarone or verapamil compared with usual care in symptomatic patients hospitalized with confirmed COVID-19 infection.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: Amiodarone; Drug: Verapamil

• Study Type: Interventional
• Enrollment (Actual): 804
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Poland
  • Bydgoszcz, Poland
    • Nicolaus Copernicus University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Hospitalized patients with confirmed COVID-19 infection and symptoms, with an oxygenation index defined as quotient of partial pressure of oxygen in arterial blood (PaO2, in mmHg) and fraction of inspired oxygen (FiO2) > 200.

Exclusion Criteria:

• Acute respiratory distress syndrome (ARDS)
• Contraindications for or known hypersensitivity to amiodarone or calcium channel blockers
• Long QT syndrome
• Prolonged baseline QTc interval (≥450 ms).
• Cardiogenic shock or severe hypotension (SBP< 90 mmHg)
• Severe left ventricle dysfunction (left ventricular ejection fraction ≤35%)
• Severe sinus - node dysfunction with marked sinus bradycardia
• 2nd/3rd degree heart block
• Bradycardia without pacemaker that has caused syncope
• History of severe dysthyroidism
• A-Fib/flutter conducted via accessory pathway (ie,Wolff -Parkinson-White)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Usual Care
Experimental: Amiodarone; Amiodarone - administered intravenously Bolus of 150 mg is given over a minimum of 10 min, with subsequent continuous infusion of 1 mg/min for 6 h, next continuous infusion of 0.5 mg/min for 18 h, then switch to oral administration. Oral administration 200 to 400 mg/day (adjust dosage based on cardiac response and age) up to discharge.	Drug: Amiodarone; Ion channel blocker
Experimental: Verapamil; Verapamil - administered intravenously Bolus of 0.075-0.15 mg/kg (5-10 mg) over at least 3 minutes, then switch to oral administration. Oral administration 120 to 480 mg/day in divided doses every 6-8 hours (adjust dosage based on cardiac response and age) up to discharge.	Drug: Verapamil; Ion channel blocker

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical improvement	Time to first occurrence of clinical improvement assessed on a seven category scale ranging from 1 to 7	Randomization to day 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical improvement	Time to first occurrence of clinical improvement assessed on a seven category scale ranging from 1 to 7	Randomization to day 7 and 28
Cardiac troponins	assessed serially	7, 10 and 15 days after randomization
Mortality	Individual endpoint	Randomization to day 28
Time to resolution of fever	Defined as body temperature (≤36.6°C [axilla], or ≤37.2 °C [oral], or ≤37.8°C [rectal]) for at least 48 hours without antipyretics or until discharge, whichever is sooner.	Randomization to day 28
Tachyarrhythmias	defined as atrial fibrillation, supraventricular or ventricular tachycardia requiring treatment	Randomization to day 28
Time to clinical improvement from admission using the 7-point ordinal scale	Clinical improvement assessed on a seven category scale ranging from 1 to 7.	Randomization to day 28
Change in NEWS2 score	The National Early Warning Score (NEWS2) score. A Higher score is worse.	Randomization to day 7 and 15
Duration of hospitalization	Length of hospitalization in days	Randomization to day 28
PO2/FIO2	oxygenation index defined as quotient of partial pressure of oxygen in arterial blood (PaO2, in mmHg) and fraction of inspired oxygen (FiO2)	Randomization to day 7 and 15

Collaborators and Investigators

• Sponsor: Nicolaus Copernicus University

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2020
• Primary Completion (Actual): May 25, 2021
• Study Completion (Actual): June 5, 2021

Study Registration Dates

• First Submitted: April 14, 2020
• First Submitted That Met QC Criteria: April 16, 2020
• First Posted (Actual): April 17, 2020

Study Record Updates

• Last Update Posted (Actual): September 5, 2021
• Last Update Submitted That Met QC Criteria: August 30, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Vasodilator Agents; Enzyme Inhibitors; Membrane Transport Modulators; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Sodium Channel Blockers; Cytochrome P-450 CYP2D6 Inhibitors; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Cytochrome P-450 CYP1A2 Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Potassium Channel Blockers; Verapamil; Amiodarone
• Other Study ID Numbers: NCU-COVID19

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No