A Study to Select the Dose and Evaluate the Effectiveness and Safety of the Drug Refralon®, Tablets, 1 mg for Long-term Use to Prevent Recurrence of Atrial Fibrillation/Flutter After Terminating Its Persistent Form

NCT06540352 | Active Not Recruiting Phase 2

• 1 other identifier: REF-II-08-2023
• Study Type: interventional
• Target: 175
• Locations: 1 country
• Sites: 1

Brief Summary

Refralon® tablets in two different doses (1 or 2 tablets per day) will be evaluated vs. placebo in patients with persistent atrial fibrillation/flutter after synus rhythm restoration in order to prevent recurrence of arrhythmia. Efficacy and safety of Refralon® tablets will be studied, its optimal dose will be selected and its pharmacokinetics will be evaluated in 14 days, 1, 3 and 6 months.

Conditions

Atrial Fibrillation; Atrial Flutter

Keywords

Refralon; Cavutilide; Niferidil; class III antiarrhythmic drug; new Russian drug; atrial fibrillation (AF); tablet; atrial flutter (AFL)

Outcome Measures

Primary Outcomes (1)

• Proportion of subjects in the group who were shown to maintain sinus rhythm at the end of 6 months of follow-up;

  6 months

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Drug: Mannitol

1 mg

EXPERIMENTAL

Drug: 4-Nitro-N-[(1RS)-1-(4-fluorophenyl)-2-(1-ethylpiperidin-4-yl)ethyl]benzamide hydrochloride

2 mg

EXPERIMENTAL

Drug: 4-Nitro-N-[(1RS)-1-(4-fluorophenyl)-2-(1-ethylpiperidin-4-yl)ethyl]benzamide hydrochloride

Interventions

Mannitol DRUG

Placebo in tablets

Placebo

4-Nitro-N-[(1RS)-1-(4-fluorophenyl)-2-(1-ethylpiperidin-4-yl)ethyl]benzamide hydrochloride DRUG

The drug Refralon® (n-1-\[(4-fluorophenyl)-2-(1-ethyl-4-piperidyl)-ethyl\]-4-nitrobenzamide hydrochloride) in the dosage form of a concentrate for the preparation of a solution for intravenous administration is registered for medical use in RF June 24, 2014, re-registration was successfully completed on November 20, 2019, registration certificate LP 002510, until December 31, 2025.

1 mg; 2 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Persistent form of AF/AFL lasting 7 days - 1 year (including patients who have previously undergone ineffective catheter or surgical ablation of AF or AFL and patients with a pacemaker or implanted cardioverter-defibrillator (ICD));
• Basic rhythm - AF and/or AFL according to the results of 12-lead ECG at randomization (Visit 2);
• Left ventricular ejection fraction (LVEF) \>40% according to the Simpson method;

You may not qualify if:

• Intake of class IA, IC and class III antiarrhythmic drugs less than 7 days (for amiodarone less than 60 days) before the study drug intake;
• History of myocardial infarction or other structural heart disease;
• QT prolongation over 500 ms.

Sponsors & Collaborators

• National Medical Research Center for Cardiology, Ministry of Health of Russian Federation: lead

Study Sites (1)

National Medical Research Center for Cardiology, Ministry of Health of Russian Federation Organization

Moscow, Russia

Location

Related Publications (8)

• Beliaeva MM, Dzaurova KM, Yuricheva YA, Novikov PS, Mironov NY, Tarasovskiy GS, Zelberg MA, Sokolov SF, Golitsyn SP. Intravenous Cavutilide for Pharmacological Conversion of Paroxysmal and Persistent Atrial Fibrillation in Patients with Heart Failure. J Cardiovasc Dev Dis. 2023 Dec 6;10(12):487. doi: 10.3390/jcdd10120487.

  PMID: 38132655 BACKGROUND

• Abramochkin DV, Pustovit OB, Mironov NY, Filatova TS, Nesterova T. Characterization of hERG K+ channel inhibition by the new class III antiarrhythmic drug cavutilide. Naunyn Schmiedebergs Arch Pharmacol. 2024 Jul;397(7):5093-5104. doi: 10.1007/s00210-023-02940-5. Epub 2024 Jan 15.

  PMID: 38224347 BACKGROUND

• Egorov YV. Atypical Antiadrenergic Effect of Refralon as a Mechanism of High Antiarrhythmic Effectiveness. Bull Exp Biol Med. 2024 May;177(1):57-62. doi: 10.1007/s10517-024-06131-x. Epub 2024 Jul 2.

  PMID: 38954299 BACKGROUND

• Gagloeva DA, Dzaurova KM, Zelberg MA, Mironov NY, Yuricheva YA, Sokolov SF, Golitsyn SP. Early initiation of anti-relapse antiarrhythmic therapy in patients with atrial fibrillation and flutter after pharmacological cardioversion with refralon. Kardiologiia. 2023 Jun 30;63(6):21-27. doi: 10.18087/cardio.2023.6.n2276. English, Russian.

  PMID: 37470730 BACKGROUND

• Abramochkin DV, Pustovit OB, Mironov NY, Filatova TS, Kuzmin VS. The Dependence of the Electrophysiological Effects of Class III Antiarrhythmic Drug Refralon on the Frequency of Myocardium Activation. Bull Exp Biol Med. 2023 Mar;174(5):610-615. doi: 10.1007/s10517-023-05756-8. Epub 2023 Apr 11.

  PMID: 37040036 BACKGROUND

• Dzaurova KM, Mironov NY, Yuricheva YA, Vlodzyanovsky VV, Mironova NA, Laiovich LY, Malkina TA, Zinchenko LV, Sokolov SF, Golitsyn SP. [Efficiency and safety of using the modified protocol for the administration of the domestic class III antiarrhythmic drug for the relief of paroxysmal atrial fibrillation]. Ter Arkh. 2021 Sep 15;93(9):1052-1057. doi: 10.26442/00403660.2021.09.201008. Russian.

  PMID: 36286864 BACKGROUND

• Golitsyn SP, Saidova MA, Sokolov SF, Vlodzyanovskiy VV, Malkina TA, Rozenshtraukh LV, Chazov EI. [Restoration of Sinus Rhythm in Patients With Persistent Atrial Fibrillation and Obesity: New Possibilities of Pharmacological Cardioversion]. Kardiologiia. 2017 Oct;57(10):80-86. doi: 10.18087/cardio.2017.10.10036. Russian.

  PMID: 29276933 BACKGROUND

• Maykov EB, Yuricheva YA, Mironov NY, Sokolov SF, Golitsyn SP, Rozenshtraukh LV, Chazov EI. [Refralon (niferidil) is a new class III antiarrhythmic agent for pharmacological cardioversion for persistent atrial fibrillation and atrial flutter]. Ter Arkh. 2015;87(1):38-48. doi: 10.17116/terarkh201587138-48. Russian.

  PMID: 25823268 BACKGROUND

Related Links

• Russian registry of clinical trials record

MeSH Terms

Conditions

Atrial Fibrillation; Atrial Flutter

Interventions

Mannitol

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2024
• First Posted: August 6, 2024
• Study Start: June 3, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)