Trimetazidine Therapy in Hypertrophic Cardiomyopathy
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.
Other: Placebo capsule
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||A Phase 2b Randomised, Double Blind, Placebo-controlled Trial of Trimetazidine Therapy in Patients With Non-obstructive Hypertrophic Cardiomyopathy|
- Peak oxygen consumption [ Time Frame: 3 months ] [ Designated as safety issue: No ]
- Left ventricular function [ Time Frame: 3 months ] [ Designated as safety issue: No ]TDI and 2D strain
- Symptom status [ Time Frame: 3 months ] [ Designated as safety issue: No ]questionnaire
- Arrhythmia [ Time Frame: 3 months ] [ Designated as safety issue: No ]24 Hour Holter
- Cardiac biomarkers [ Time Frame: 3 months ] [ Designated as safety issue: No ]
- Exercise capacity [ Time Frame: 3 months ] [ Designated as safety issue: No ]6 minute walk test
|Study Start Date:||April 2012|
|Estimated Study Completion Date:||April 2014|
|Estimated Primary Completion Date:||April 2014 (Final data collection date for primary outcome measure)|
|Active Comparator: Trimetazidine||
Trimetazidine 20mg three times per day for 3 months
|Placebo Comparator: Placebo capsule||
Other: Placebo capsule
one capsule three times per day for 3 months
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.
|Contact: Perry M Elliott, MBBS MD||020 3456 email@example.com|
|Contact: Caroline J Coats, MBBS||020 3456 firstname.lastname@example.org|
|The Heart Hospital, UCLH||Recruiting|
|London, United Kingdom, W1G 8PH|
|Principal Investigator:||Perry M Elliott, MBBS MD||University College, London|