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

• ClinicalTrials.gov Identifier: NCT04351763
• Recruitment Status: Completed
• First Posted: April 17, 2020
• Last Update Posted: September 5, 2021
• Sponsor: Nicolaus Copernicus University
• Information provided by (Responsible Party): Eliano Pio Navarese, Nicolaus Copernicus University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
COVID-19	Drug: Amiodarone; Drug: Verapamil	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 804 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: parallel group, randomized trial
• Masking: Single (Outcomes Assessor)
• Masking Description: Clinical events will be validated blindly by an independent clinical event committee (CEC) unaware of the treatment allocation.
• Primary Purpose: Treatment
• Official Title: Amiodarone or Verapamil in COVID-19 Hospitalized Patients With Symptoms
• Actual Study Start Date: May 20, 2020
• Actual Primary Completion Date: May 25, 2021
• Actual Study Completion Date: June 5, 2021

Arms and Interventions

Arm	Intervention/treatment
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
No Intervention: Usual Care

Outcome Measures

Primary Outcome Measures :

1. Clinical improvement [ Time Frame: Randomization to day 15 ]
   Time to first occurrence of clinical improvement assessed on a seven category scale ranging from 1 to 7

Secondary Outcome Measures :

1. Clinical improvement [ Time Frame: Randomization to day 7 and 28 ]
   Time to first occurrence of clinical improvement assessed on a seven category scale ranging from 1 to 7
2. Cardiac troponins [ Time Frame: 7, 10 and 15 days after randomization ]
   assessed serially
3. Mortality [ Time Frame: Randomization to day 28 ]
   Individual endpoint
4. Time to resolution of fever [ Time Frame: Randomization to day 28 ]
   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.
5. Tachyarrhythmias [ Time Frame: Randomization to day 28 ]
   defined as atrial fibrillation, supraventricular or ventricular tachycardia requiring treatment
6. Time to clinical improvement from admission using the 7-point ordinal scale [ Time Frame: Randomization to day 28 ]
   Clinical improvement assessed on a seven category scale ranging from 1 to 7.
7. Change in NEWS2 score [ Time Frame: Randomization to day 7 and 15 ]
   The National Early Warning Score (NEWS2) score. A Higher score is worse.
8. Duration of hospitalization [ Time Frame: Randomization to day 28 ]
   Length of hospitalization in days
9. PO2/FIO2 [ Time Frame: Randomization to day 7 and 15 ]
   oxygenation index defined as quotient of partial pressure of oxygen in arterial blood (PaO2, in mmHg) and fraction of inspired oxygen (FiO2)

Eligibility Criteria

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

Criteria

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)

Contacts and Locations

Locations

Poland

Nicolaus Copernicus University

Bydgoszcz, Poland

Sponsors and Collaborators

Nicolaus Copernicus University

More Information

• Responsible Party: Eliano Pio Navarese, Prof Eliano P. Navarese, MD, PhD, Nicolaus Copernicus University
• ClinicalTrials.gov Identifier: NCT04351763
• Other Study ID Numbers: NCU-COVID19
• First Posted: April 17, 2020
• Last Update Posted: September 5, 2021
• Last Verified: August 2021

• 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

Additional relevant MeSH terms:

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