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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04351763
Recruitment Status : Recruiting
First Posted : April 17, 2020
Last Update Posted : April 17, 2020
Sponsor:
Information provided by (Responsible Party):
Eliano Pio Navarese, Nicolaus Copernicus University

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

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Study Type : Interventional  (Clinical Trial)
Estimated 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
Estimated Study Start Date : April 27, 2020
Estimated Primary Completion Date : March 2, 2021
Estimated Study Completion Date : April 10, 2021

Resource links provided by the National Library of Medicine


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



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. Mean change in the 7-point ordinal scale [ Time Frame: Randomization to day 7,15 and 28 ]
    assessed on a seven category scale ranging from 1 to 7

  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. Clinical improvement or fever resolution [ Time Frame: Randomization to day 7,15 and 28 ]
    Composite endpoint

  6. Tachyarrhythmias [ Time Frame: Randomization to day 28 ]
    defined as atrial fibrillation, supraventricular or ventricular tachycardia requiring treatment

  7. Mortality or tachyarrhythmias [ Time Frame: Randomization to day 28 ]
    Composite endpoint

  8. 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.

  9. Change in NEWS2 score [ Time Frame: Randomization to day 7 and 15 ]
    The National Early Warning Score (NEWS2) score. A Higher score is worse.

  10. Duration of hospitalization [ Time Frame: Randomization to day 28 ]
  11. 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)

  12. Clinical improvement [ Time Frame: Randomization to day 15 ]
    Assessed on a modified seven category scale ranging from 1 to 7



Information from the National Library of Medicine

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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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04351763


Contacts
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Contact: Prof. Eliano P Navarese, MD, PhD +48 885 101 728 elianonavarese@gmail.com
Contact: Prof. Jacek Kubica, MD, PhD +48 885 101 728 jkubica@cm.umk.pl

Locations
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Poland
Nicolaus Copernicus University Recruiting
Bydgoszcz, Poland
Contact: Jacek Kubica, MD, PhD       jwkubica@gmail.com   
Sponsors and Collaborators
Nicolaus Copernicus University
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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    Key Record Dates
Last Update Posted: April 17, 2020
Last Verified: April 2020

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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:
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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