Efficacy and Safety Evaluation of Refralon®, Concentrate for Solution for Intravenous Injection in Patients With Paroxysmal and Persistent Atrial Fibrillation and Flutter

R-Pharm

Status: Completed

Conditions: Paroxysmal Atrial Fibrillation; Atrial Flutter; Persistent Atrial Fibrillation

Treatments: Drug: Refralon

Study type: Observational

Funder types: Industry; Other

Identifiers

NCT05773170

CC01897112

Details and patient eligibility

About

The goal of this retrospective registry is to evaluate the efficacy and safety of Refralon®, concentrate for solution for intravenous injection, as chemical cardioversion in patients with paroxysmal and persistent atrial fibrillation and flutter in routine clinical practice. The main questions it aims to answer are:

• What is the incidence of sinus rhythm restoration within 6 hours in patients with paroxysmal atrial fibrillation (AF)/atrial flutter (AFL) after the first dose of Refralon®?
• What is the incidence of sinus rhythm restoration within 24 hours in patients with persistent AF/AFL after the first dose of Refralon®?

Full description

The registry is a retrospective multicenter observational study in patients with paroxysmal and persistent forms of AF and AFL who underwent chemical cardioversion with Refralon® in a hospital setting.

After the compliance with the inclusion criteria and the absence of exclusion criteria based on medical documentation, the patient data will be collected from medical documentation available for the analysis into a unified electronic case report form (eCRF).

Alongside the study therapy, all the patients must receive an adequate anticoagulant therapy in accordance with the current clinical guidelines of the Ministry of Health of the Russian Federation. After chemical cardioversion, patients were followed up and examined as a part of routine clinical practice. The examination data will be used for this study analysis. No additional therapeutic or diagnostic procedures are provided by the analysis protocol.

Study patient follow-up period was 24 hours from the Refralon® first dose administration.

The patients' data collection is planned for 8 months. It is planned to enroll 1500 patients with persistent and paroxysmal AF and AFL, meeting the inclusion/exclusion criteria. If necessary, it is possible to extend the registry data collection period to include the planned number of patients.

Approximately in 3 and 6 months from the registry initiation (but not earlier than after the inclusion of 150 patients into the registry), an interim collected data analysis can be performed in order to preliminary assess the Refralon® efficacy and safety data in this study, as well as to identify the potential data entry errors.

Enrollment: 1,147 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis: paroxysmal or persistent atrial fibrillation or flutter;
• A chemical cardioversion procedure performed with Refralon® in a hospital setting.

Exclusion criteria

• Congenital or acquired QT interval prolongation in the electrocardiogram (ECG) in 12 standard leads for more than 440 ms at the time of cardioversion;
• Bradysystolic atrial fibrillation or flutter (mean heart rate < 50 bpm or pauses > 3 sec, registered on the ECG or identified by the results of 24-hour Holter ECG monitoring, except for the cases of its correction by a cardiac pacemaker at the time of cardioversion;
• Sick sinus syndrome (sinus bradycardia, sinoatrial blockade), previously registered as associated with sinus rhythm, except for the cases of its correction with a cardiac pacemaker at the time of cardioversion;
• Degree II - III atrioventricular blockade, two- and three-beam blockade with no cardiac pacemaker at the time of cardioversion;
• Acute myocardial infarction period at the time of cardioversion;
• Acute period after coronary artery bypass grafting (CABG) or other cardiac surgery (at least 7 days after CABG at the time of cardioversion);
• Decompensated or severe chronic heart failure (III-IV functional class according to New York Heart Association (NYHA) classification) at the time of cardioversion;
• Uncontrolled bronchial asthma, severe respiratory failure at the time of cardioversion;
• Pregnancy and breastfeeding at the time of cardioversion;
• Administration of Class IA antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide, procainamide) at the time of cardioversion;
• Class III antiarrhythmic drugs administration at the time of cardioversion;
• Cardiac glycosides administration at the time of cardioversion;
• Administration of QT-prolonging drugs at the time of cardioversion;
• Heart rate < 50 bpm, pauses > 3 seconds on the ECG or Holter ECG monitoring (HM-ECG) during wakefulness at the time of cardioversion;
• Hyperthyroidism or decompensated hypothyroidism (thyroid stimulating hormone (TSH) < lower limit of normal or > 2 upper limits of normal) at the time of cardioversion;
• Uncorrectable electrolyte disorders (potassium level less than 3.5 mmol/L) at the time of cardioversion;
• Identified contraindications to the sinus rhythm restoration at the time of cardioversion;
• Blood clots in the heart cavities or spontaneous grade III-IV echo contrast at the time of cardioversion according to transesophageal echocardiography;
• The need for electrical cardioversion due to the patient's hemodynamic instability at the time of cardioversion.

Trial design

1,147 participants in 1 patient group

Pharmacological cardioversion with Refralon

Description:

1. Refralon® 0.1% solution administration at a dose of 10 μg/kg of body weight intravenously (IV) for 2-3 minutes; It is allowed to divide the first Refralon® bolus into two consecutive injections: the first dose administration - 5 μg/kg of body weight, if the AF/AFL persists, administer the second dose - 5 μg/kg of body weight (total dose 10 μg/kg) in 15 minutes. 2. If no effect is registered (no sinus rhythm restoration), repeat IV administration of Refralon® 0.1% solution at a dose of 10 μg/kg of body weight (total dose: 20 μg/kg of body weight) in 15 minutes; 3. If no effect is registered, repeat IV administration of Refralon® 0.1% solution at a dose of 10 μg/kg of body weight (total dose: 30 μg/kg of body weight) in 15 minutes. In case of AF/AFL recurrence after the sinus rhythm restoration (with no contraindications), it is possible to re-administer Refralon®, while the maximum total drug daily dose (from the first administration) should not exceed 30 μg/kg of body weight.

Treatment:

Drug: Refralon