Trimetazidine Therapy in Hypertrophic Cardiomyopathy

Study Overview
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Brief Summary
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Hypertrophic cardiomyopathy (HCM) is a common inherited heart condition that causes breathlessness, chest pain and fatigue. There are few treatments available. The investigators have recently shown that a drug called perhexiline reduced symptoms and improved exercise capacity in patients with HCM. This change appears to be driven by alterations in myocardial energy metabolism. The aim of this trial is to test a similar drug, trimetazidine, in a group of symptomatic patients with non-obstructive HCM. HYPOTHESIS: trimetazidine will improve symptoms, peak oxygen consumption, cardiac function and arrhythmia burden in medically refractory symptomatic patients with non-obstructive HCM.

Detailed Description
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BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a common inherited disorder of heart muscle affecting 1 in 500 individuals worldwide. It is associated with arrhythmias, heart failure and sudden death in young people. In the majority of patients, HCM is caused by mutations in genes encoding cardiac contractile proteins. It has been hypothesised that excessive sarcomeric energy consumption is an important and early factor in the pathophysiology of HCM. Therefore modulation of myocardial metabolism presents a novel target for improving myocardial performance and symptoms in patients with HCM. Trimetazidine is an anti-anginal agent which like perhexiline reduces fatty acid oxidation and increases glucose oxidation, thus increasing the efficiency of energy production. Trimetazidine has been shown to significantly improve exercise performance in patients with stable angina, ischaemic and non ischaemic cardiomyopathy, either as monotherapy or in combination with beta-blockers or calcium channel blockers, DESIGN: A single centre prospective randomised, double blind, placebo-controlled, trial of trimetazidine therapy. DOSING: 20 mg Trimetazidine or Placebo three times daily for three months METHODS: The following assessments will be made at baseline and after 3 months treatment: history and physical examination, Minnesota heart failure questionnaire, fasting blood tests, electrocardiogram, echocardiogram, cardiopulmonary exercise test, six minute walk test, 24 hour ECG Holter monitor.

Official Title
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A Phase 2b Randomised, Double Blind, Placebo-controlled Trial of Trimetazidine Therapy in Patients With Non-obstructive Hypertrophic Cardiomyopathy

Conditions
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Hypertrophic Cardiomyopathy

Intervention / Treatment
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* Drug: Trimetazidine
* Other: Placebo capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-obstructive hypertrophic cardiomyopathy (gradient <30 mmHg at rest) NYHA (New York Heart Association) Class ≥ 2 Peak VO2 (maximal oxygen consumption) ≤80% predicted for age and gender Heart rate < 90/minute at rest Exclusion Criteria: Diabetes Mellitus Abnormal renal function (GFR<60ml/min) or hepatic impairment Female who is pregnant, lactating or planning pregnancy during the course of the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Trimetazidine<br> | Drug: Trimetazidine<br>* Trimetazidine 20mg three times per day for 3 months<br>|
| Placebo Comparator: Placebo capsule<br> | Other: Placebo capsule<br>* one capsule three times per day for 3 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak oxygen consumption |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left ventricular function | TDI and 2D strain | 3 months | 
| Symptom status | questionnaire | 3 months | 
| Arrhythmia | 24 Hour Holter | 3 months | 
| Cardiac biomarkers |  | 3 months | 
| Exercise capacity | 6 minute walk test | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Trimetazidine