Refralon Versus Amiodarone for Cardioversion of Paroxysmal Fibrillation and Atrial Flutter

Phase 4

Completed

• Conditions: Atrial Fibrillation Paroxysmal
• Interventions: Drug: Pharmacological cardioversion with Refralon; Drug: Pharmacological cardioversion with Amiodarone

• Registration Number: NCT05445297
• Lead Sponsor: National Medical Research Center for Cardiology, Ministry of Health of Russian Federation

Brief Summary

Patients hospitalized with paroxysmal atrial fibrillation and flutter to restore sinus rhythm will be randomized into two groups: one will be cardioversion with refralon and the other with amiodarone

Detailed Description

Atrial fibrillation (AF) and flutter (AFL) are the most common types of arrhythmia in clinical practice. Both electrical and medical cardioversion can be used to restore sinus rhythm. Currently, the most studied and commonly used drug for pharmacological cardioversion of paroxysms of AF/AFL is amiodarone, which belongs to class III antiarrhythmic drugs. The highest recovery rates of sinus rhythm (SR) (\>90%) are achieved with intravenous administration of amiodarone at a dose of more than 1500 mg / day or up to a maximum of 3000 mg / day. However, most commonly, amiodarone is used at a standard dose of 5 mg/kg body weight, with an efficacy of 34-69%. In 2014, a new Russian class III antiarrhythmic drug, Refralon, was registered. In 2020, the drug was included in the National Clinical Guidelines "Atrial Fibrillation and Flutter", approved by the Ministry of Health of the Russian Federation. When using refralon in doses from 10 to 30 μg/kg, SR recovery was noted in 91.6% of patients with persistent AF/AFL in 50% of patients SR restored within 15 minutes from the start of the drug administration.

Randomized trials comparing the efficacy and safety of refralon with other antiarrhythmic drugs have not been conducted. It is extremely important to directly compare the efficacy and safety of these two drugs in patients with paroxysmal AF in a prospective randomized study.

Study Timeline

• Study Start: 2022-01-26
• Study First Submitted: 2022-06-27
• Study First Submitted QC: 2022-07-05
• Study First Posted: 2022-07-06
• Primary Completion: 2023-06-30
• Study Completion: 2023-06-30
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-24
• Last Update Posted: 2025-03-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. Paroxysmal form of AF/AFL;
2. Indications for SR recovery

Exclusion Criteria

1. Arrhythmogenic effect of refralon, amiodarone and other antiarrhythmic drugs in history;
2. Chronic kidney disease with a decrease in glomerular filtration rate less than 30 ml / min / 1.73 m2;
3. Chronic heart failure (functional class IV);
4. Atrioventricular blockade of 2-3 degrees (with the exception of patients with an implanted pacemaker);
5. Dysfunction of the sinoatrial node (with the exception of patients with an implanted pacemaker);
6. Bradysystolic atrial fibrillation (heart rate <50 beats/min);
7. Duration of the QT interval >440 ms;
8. Hemodynamic instability requiring emergency cardioversion;
9. Contraindications to anticoagulant therapy;
10. Thyrotoxicosis or decompensated hypothyroidism;
11. Uncorrected electrolyte disturbances at the time of cardioversion (potassium level less than 3.5 mmol/l);
12. Pregnancy and breastfeeding period.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Refralon group	Pharmacological cardioversion with Refralon	-
Amiodarone group	Pharmacological cardioversion with Amiodarone	-

Primary Outcome Measures

Name	Time	Method
Sinus rhythm recovery time	24 hours	The time elapsed from the start of drug administration to recovery of SR
Ventricular arrhythmogenic effect	24 hours	Registration of sustained and nonsustained (3 or more QRS) ventricular tachycardia or ventricular fibrillation after administration of drug (refralon/amiodarone)
Bradyarrhythmias (pauses and bradycardia)	24 hours	Decrease in heart rate to less than 50bpm after administration of drug (refralon/amiodarone) during AF or after restoration of SR - the minimum heart rate, the duration of the maximum recorded pause and the time during which the heart rate was less than 50bpm will be recorded
Arterial hypotension	24 hours	Decrease in blood pressure by more than 20 mm Hg from the initial value(if asymptomatic) after administration of drug (refralon/amiodarone) or by more than 10 mm Hg (if symptomatic)
Any clinical manifestations	24 hours	The appearance of any clinical manifestations after administration of drug (refralon/amiodarone) that are interpreted by the doctors of the intensive care unit as a worsening of patient's clinical status.
Number of patients who recovered sinus rhythm after the minimum dose of refralon.	24 hours	Number of patients who recovered SR when using refralon at a dose of 5 µg/kg.
Increased QT interval (more than 500 ms)	24 hours	The number of patients who have an increase in the QT interval (more than 500 ms) and the time during which the duration of the QT interval exceeded 500 ms.
Restoration of sinus rhythm	24 hours	Restoration of SR within 24 hour from the start of drug administration (refralon/amiodarone).
Recurrent AF/AFL after successful cardioversion	24 hours	Absence of sustained (more than 30 seconds) recurrences of AF/AFL within 24 hours after successful cardioversion;

Trial Locations

Locations (1)

Federal State Budgetary Institution NATIONAL MEDICAL RESEARCH CENTRE OF CARDIOLOGY NAMED AFTER ACADEMICIAN E.I.CHAZOV. of the Ministry of Health of the Russian Federation; 🇷🇺 Moscow, Russian Federation