Treatment Effects of Bisoprolol and Verapamil in Symptomatic Patients With Non-obstructive Hypertrophic Cardiomyopathy
Status:
Recruiting
Trial end date:
2025-06-01
Target enrollment:
Participant gender:
Summary
Aim: To compare treatment effects of Bisoprolol and Verapamil in 140 patients with
non-obstructive hypertrophic cardiomyopathy. The overall clinical purpose is to reduce the
symptomatic burden and arrhythmic complications.
Background: Hypertrophic cardiomyopathy (HCM) is characterized by hypertrophy of the left
ventricular wall and a hypercontracted state of the sarcomeres. This narrows the left
ventricular cavity, but though the left ejection fraction is increased the stroke volume and
the cardiac output cannot be fully compensated. The disease manifestiations can be mild or
develop into severe functional limitations and devasting complications at early age. Dyspnea,
chest pain, palpitations and syncope are the most common symptoms, and patients are at risk
of supraventricular and ventricular arrhythmias. Arrhythmias and sudden cardiac deaths may
precede heart failue symptoms. Patients with symptomatic HCM are treated initially with beta
blockers and calcium channel blockers. However, there is limited evidence supporting the
effectiveness of this guideline-recommended treatment in HCM.
Methods: The study is a multicenter, double-blinded, randomized, placebo-controlled
cross-over trial. Patients are randomized in to three 35-days treatment periods with
Bisprolol, Verapamil and Placebo. Each treatment period includes a 7-days up titration
period, a 21-days target dose period and a 7-days down titration period. Between treatment
periods 1-30 days treatment pause is allowed. End point will be evaluated at day 21 +/- 4
days. Patients will be evaluated by cardiopulmonary exercise test, echocardiography, 7 day
Holter-monitoring, biomarkers and the Kansas City Cardiomyopathy Questionnaire (KCCQ). A
subgroup of patients will also be evaluated with cardiac magnetic resonance imaging.
Hypotheses: Three equal independent primary effect parameters will be analyzed between
treatment with Bisoprolol and Verapamil:
1. The incidence of non-sustained ventricular tachycardia (NSVT) is different between
treatment in non-obstructive HCM patients.
2. The left ventricular outflow tract (LVOT) time velocity integral (VTI) is different
between treatment in non-obstructive HCM patients.
3. The maximal oxygen consumption (VO2 max) is different between treatments in
non-obstructive HCM patients.
Phase:
Phase 4
Details
Lead Sponsor:
Morten Steen Kvistholm Jensen
Collaborators:
Bispebjerg Hospital Gentofte University Hospital Odense University Hospital Rigshospitalet, Denmark Viborg Regional Hospital Zealand University Hospital