Amiodarone or Verapamil in COVID-19 Hospitalized Patients With Symptoms

Study Overview
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Brief Summary
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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.

Official Title
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Amiodarone or Verapamil in COVID-19 Hospitalized Patients With Symptoms

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Amiodarone
* Drug: Verapamil


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: parallel group, randomized trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amiodarone<br>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<br>* Ion channel blocker<br>|
| Experimental: Verapamil<br>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<br>* Ion channel blocker<br>|
| No Intervention: Usual Care<br> | |

What is the study measuring?
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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 |