Early ablation of atrial fibrillation in patients with hypertrophic cardiomyopathy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Narodowy Instytut Kardiologii Stefana Kardynala Wyszynskiego Panstwowy Instytut Badawczy

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

completed 16 Sep 2025

Decision date (initial)

2024-03-04

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The aim of the study is to compare 3 strategies (2 based on pharmacotherapy and invasive methods of early ablation) to prevent recurrence of atrial fibrillation (AF) in patients
diagnosed with hypertrophic cardiomyopathy (HCM). more effective than two alternative pharmacotherapy strategies compared in the study: 1. use of amiodarone or 2. only
beta-blocker or sotalol.
Population: 725 patients diagnosed with HCM will be included in the observation phase of the study and subsequently 300 with documented AF > 30 sec. episode will be
included in randomized therapeutic intervention phase.

Conditions and MedDRA coding

Hypertrophic cardiomyopathy (HCM) is the most common genetically determined disease of the heart, characterized by a varied picture and clinical course. The first comprehensive clinical description of the disease comes from the 1960s. Currently, the disease is diagnosed on the basis of a phenotypic picture showing left ventricular hypertrophy, which cannot be explained by the increased hemodymamic overload only. Observed hypertrophy (up to 30 to 50 mm) in some cases presents smaller (from 13 to 7 / 70 14 mm among family members), what may sometimes require differentiation from hypertrophy secondary to arterial hypertension or the physiological athlete heart phenomenon. Epidemiological studies have shown the incidence of the disease 1 per 500 people in the general population, but taking into account the clinical and genetic diagnosis, the incidence may reach even 1 per 200. It can be estimated that in Poland about 100,000 people may be affected by HCM, and only a part of them is diagnosed, mostly using imaging methods. Worldwide, HCM is likely to affect around 20 million people, come across a wide range of ethnicities and races, and affects both genders equally. Hypertrophic cardiomyopathy is an inherited disease in an autosomal dominant manner and is most often associated with mutations in one of described several genes coding for sarcomere proteins. Atrial fibrillation (AF) occurs in 20-25% of patients with hypertrophic cardiomyopathy, and the annual incidence of AF in HCM ranges from 2% to 3%. the reference center was 25.5%. The incidence of AF in patients with hypertrophic cardiomyopathy under 65 years of age in own data of the National Institute of Cardiology, was found to be as high as 25.5%. In elderly population, AF occurence is even higher, with respect to the high frequency and importance of this clinical problem for highly specialized centers. Due to the development of technologies for continuous ECG monitoring and the resulting changes in the sensitivity and specificity of AF diagnosis, the real AF occurrence in the population with HCM may be as high as 40-50%. At the same time, current studies indicate that AF significantly affects the prognosis of patients with HCM and the occurrence of any form of AF is associated with a significantly increased risk of systemic embolism (including CNS stroke) [relative risk (RR) 7.0; 95% CI 4.6-10.7], heart failure progression (RR 2.8; 95% CI 1.6-4.6), sudden cardiac death (RR 1.7; 95% CI 1.3-2 , 3) and all-cause mortality (RR 2.5; 95% CI 1.8-3.4) with a mean follow-up of 7 years. Hence, preventing the development of AF in patients with HCM seems to be an important therapeutic goal in this group. According to the recommendations of the Cardiac Societies worldwide, percutaneous ablation of AF can be considered in patients without significant left atrial enlargement, who have symptoms despite treatment, or who cannot take antiarrhythmic drugs or is a preferential choice. Currently, there are no prospective randomized trials of antiarrhythmic drugs versus ablation, what seems a significant limitation of all publications and recommendations regarding the treatment of AF in patients with HCM. The best and robust available registry data indicate that the initial attempt to maintain sinus rhythm with lifestyle modification and antiarrhythmic drugs is moderately successful and indicate potentially significant ablation efficacy; especially in the early stage of AF development in patients with HCM. The rationale we present led to the design of the submitted study.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1.diagnosed hypertrophic cardiomyopathy as defined by the European Society of Cardiology, 2. signed informed consent to participate in the study, 3. 18 years of age or more

Exclusion criteria 1

1. 1. age <18 years of age, 2. permanent atrial fibrillation, 3. previous treatment with amiodarone, 4. absolute contraindications to ablation treatment or absolute contraindications to amiodarone administration, 5. left atrium size in short axis echocardiography > 5.5 cm or four-chamber view LA area> 35 cm2, 6. NYHA class IV heart failure, 7. double-determined left ventricular ejection fraction <30% despite optimal treatment; including at least 1 record on sinus rhythm, 8. pregnancy or breastfeeding, 9. participation in another clinical trial, 10. expected non-compliance during the study, 11. absolute contraindication to magnetic resonance imaging, 12. other important reason which, due to the researcher opinion, does not qualify the patient to participate in the study 13.Lack of consent to use contraception during the study and during the obligatory period to use contraception after the study for one month. 14.Decompensated thyroid dysfunction 15.• Indication for simultaneous use of drugs that prolong the QT interval ((class Ia antiarrhythmic drugs, e.g.: quinidine, procainamide, disopyramide; class III antiarrhythmic drugs, e.g. sotalol, bretylium; erythromycin, cotrimoxazole, pentamidine; some antipsychotics or antidepressants, e.g. chlorpromazine, thioridazine, fluphenazine, pimozide, haloperidol, amisulpride and sertindole; lithium preparations and tricyclic drugs, e.g. doxepin, maprotiline, amitriptyline, some antihistamines, e.g. terfenadine, astemizole, mizolastine)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. death or 2. stroke / TIA or 3. extra-scheduled medical intervention defined as: hospitalization / emergency room / emergency room visit / medical visit

Secondary endpoints 1

1. 1. atrial fibrillation load> 12 hours during any observation day, 2. mean fibrillation load during the follow-up period, 4. occurrence of silent AF in the HCM patient population, 5. occurrence of ventricular arrhythmias, including non-sustained ventricular tachycardia, 6. new ischemic changes in CNS MRI, 7. correlation of changes in MRI of the CNS with the AF burden, and: 8. change in quality of life assessed by the SF-36 questionnaire before and after one year after randomization.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Narodowy Instytut Kardiologii Stefana Kardynala Wyszynskiego Panstwowy Instytut Badawczy

Sponsor organisation

Narodowy Instytut Kardiologii Stefana Kardynala Wyszynskiego Panstwowy Instytut Badawczy

Address

Alpejska 42

City

Warsaw

Postcode

04-628

Country

Poland

Scientific contact point

Organisation

Narodowy Instytut Kardiologii Stefana Kardynala Wyszynskiego Panstwowy Instytut Badawczy

Contact name

Lukasz Szumowski

Public contact point

Organisation

Narodowy Instytut Kardiologii Stefana Kardynala Wyszynskiego Panstwowy Instytut Badawczy

Contact name

Lukasz Szumowski

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications