Trimetazidine Therapy in Hypertrophic Cardiomyopathy

Hypertrophic Cardiomyopathy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01696370
• Other study ID #: 10/0216
• Status: Recruiting
• Phase: Phase 2
• First received: September 27, 2012
• Last updated: February 27, 2013
• Start date: April 2012
• Est. completion date: April 2014

Study information

• Verified date: August 2011
• Source: University College, London
• Contact: Perry M Elliott, MBBS MD
• Phone: 020 3456 7898
• Email: p.elliott[@]ucl.ac.uk
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: April 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Hypertrophic
• Hypertrophic Cardiomyopathy
• Hypertrophy

Intervention

Drug:
• Trimetazidine
Trimetazidine 20mg three times per day for 3 months

Other:
• Placebo capsule
one capsule three times per day for 3 months

Locations

Country	Name	City	State
United Kingdom	The Heart Hospital, UCLH	London

Sponsors (2)

Lead Sponsor	Collaborator
University College, London	British Heart Foundation

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Peak oxygen consumption		3 months	No
Secondary	Left ventricular function	TDI and 2D strain	3 months	No
Secondary	Symptom status	questionnaire	3 months	No
Secondary	Arrhythmia	24 Hour Holter	3 months	No
Secondary	Cardiac biomarkers		3 months	No
Secondary	Exercise capacity	6 minute walk test	3 months	No