Refralon Versus Amiodarone for Cardioversion of Paroxysmal Fibrillation and Atrial Flutter

Atrial Fibrillation Paroxysmal Clinical Trial

Official title:

Prospective Randomized Study Comparing the Efficacy and Safety of Refralon and Amiodarone in Cardioversion in Patients With Paroxysmal Atrial Fibrillation and Flutter

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05445297
• Other study ID #: JCBY-2021-0007-275
• Status: Recruiting
• Phase: N/A
• Start date: January 26, 2022
• Est. completion date: March 30, 2024

Study information

• Verified date: July 2022
• Source: National Medical Research Center for Cardiology, Ministry of Health of Russian Federation
• Contact: Nikolay Yu Mironov, PhD
• Phone: 84954146151
• Email: nikmir.7ko[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: March 30, 2024
• Est. primary completion date: January 18, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Atrial Fibrillation
• Atrial Fibrillation Paroxysmal

Intervention

Drug:
• Pharmacological cardioversion with Amiodarone
Patients in this group will receive intravenous amiodarone according to the following scheme: administration of 5 mg/kg body weight of amiodarone diluted in 250 ml of 5% glucose solution intravenously for 20-60 minutes, depending on the tolerability of the drug. if there is no effect (recovery of SR did not occur within 60 minutes from the start of the drug administration), continue the infusion of amiodarone intravenously at a dose of 100 mg/hour until a total dose of 1200 mg is reached.
• Pharmacological cardioversion with Refralon
Patients in this group will receive intravenous refralon according to the following scheme: the introduction of a 0.1% solution of refralon at a dose of 5 µg per 1 kg of body weight, diluted in 20 ml of saline intravenously for 2-3 minutes; in the absence of effect (SR recovery did not occur), after 15 minutes, repeated intravenous administration of a 0.1% solution of refralon at a dose of 5 µg per 1 kg of body weight (total dose of the drug 10 µg / kg of body weight); in the absence of effect (SR recovery did not occur), after 15 minutes, the next intravenous injection of a 0.1% solution of refralon at a dose of 10 µg per 1 kg of body weight (total dose of the drug 20 µg / kg of body weight); in the absence of effect (recovery of SR did not occur), after 15 minutes, repeated intravenous administration of a 0.1% solution of refralon at a dose of 10 µg per 1 kg of body weight. Thus, the maximum total dose of the drug will be 30 µg/kg of body weight.

Locations

Country	Name	City	State
Russian Federation	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

Sponsors (1)

Lead Sponsor	Collaborator
National Medical Research Center for Cardiology, Ministry of Health of Russian Federation

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Restoration of sinus rhythm	Restoration of SR within 1 hour from the start of drug administration (refralon/amiodarone).	1 hour
Primary	Restoration of sinus rhythm	Restoration of SR within 24 hour from the start of drug administration (refralon/amiodarone).	24 hours
Primary	Number of patients who recovered sinus rhythm after the minimum dose of refralon.	Number of patients who recovered SR when using refralon at a dose of 5 µg/kg.	24 hours
Primary	Sinus rhythm recovery time	The time elapsed from the start of drug administration to recovery of SR	24 hours
Primary	Recurrent AF/AFL after successful cardioversion	Absence of sustained (more than 30 seconds) recurrences of AF/AFL within 24 hours after successful cardioversion;	24 hours
Primary	Ventricular arrhythmogenic effect	Registration of sustained and nonsustained (3 or more QRS) ventricular tachycardia or ventricular fibrillation after administration of drug (refralon/amiodarone)	24 hours
Primary	Increased QT interval (more than 500 ms)	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.	24 hours
Primary	Bradyarrhythmias (pauses and bradycardia)	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	24 hours
Primary	Arterial hypotension	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)	24 hours
Primary	Any clinical manifestations	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.	24 hours