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

• Sponsor: Nicolaus Copernicus University (Other)
• Overall Status: Completed
• CT.gov ID: NCT04351763
• Collaborator: (none)
• Enrollment: 804
• Location: 1
• Arms: 3
• Actual Duration (Months): 12.5
• Patients Per Site Per Month: 64.2

Study Details

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
• Actual Enrollment: 804 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: parallel group, randomized trialparallel 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: Jun 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 [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 [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 [7, 10 and 15 days after randomization]

   assessed serially

3. Mortality [Randomization to day 28]

   Individual endpoint

4. Time to resolution of fever [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 [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 [Randomization to day 28]

   Clinical improvement assessed on a seven category scale ranging from 1 to 7.

7. Change in NEWS2 score [Randomization to day 7 and 15]

   The National Early Warning Score (NEWS2) score. A Higher score is worse.

8. Duration of hospitalization [Randomization to day 28]

   Length of hospitalization in days

9. PO2/FIO2 [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

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	Nicolaus Copernicus University	Bydgoszcz		Poland

Sponsors and Collaborators

• Nicolaus Copernicus University

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• 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: Apr 17, 2020
• Last Update Posted: Sep 5, 2021
• Last Verified: Aug 1, 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; Amiodarone; Verapamil

Study Results

No Results Posted as of Sep 5, 2021