Clinical trial NCT01696370: Trimetazidine Therapy in Hypertrophic Cardiomyopathy
Official title: A Phase 2b Randomised, Double Blind, Placebo-controlled Trial of Trimetazidine Therapy in Patients With Non-obstructive Hypertrophic Cardiomyopathy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Hypertrophic Cardiomyopathy
Keywords: Trimetazidine
Lead sponsor: University College, London
Sponsor class: OTHER
Collaborators: name: British Heart Foundation
First posted: 2012-10-01
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Peak oxygen consumption
timeFrame: 3 months
Secondary outcomes:
measure: Left ventricular function
timeFrame: 3 months
measure: Symptom status
timeFrame: 3 months
measure: Arrhythmia
timeFrame: 3 months
measure: Cardiac biomarkers
timeFrame: 3 months
measure: Exercise capacity
timeFrame: 3 months
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: The Heart Hospital, UCLH
Study officials:
affiliation: University College, London
name: Perry M Elliott, MBBS MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Coats CJ, Pavlou M, Watkinson OT, Protonotarios A, Moss L, Hyland R, Rantell K, Pantazis AA, Tome M, McKenna WJ, Frenneaux MP, Omar R, Elliott PM. Effect of Trimetazidine Dihydrochloride Therapy on Exercise Capacity in Patients With Nonobstructive Hypertrophic Cardiomyopathy: A Randomized Clinical Trial. JAMA Cardiol. 2019 Mar 1;4(3):230-235. doi: 10.1001/jamacardio.2018.4847.