Perhexiline Therapy in Heart Failure With Preserved Ejection Fraction Syndrome

Diastolic Heart Failure Clinical Trial

Official title:

Randomised Double Blind Placebo Controlled Trial of Perhexiline in Heart Failure With Preserved Ejection Fraction Syndrome (HFpEF)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00839228
• Other study ID #: RRK 3147
• Secondary ID: RRK 3147MREC 08/
• Status: Completed
• Phase: Phase 2
• First received: February 6, 2009
• Last updated: November 4, 2015
• Start date: March 2009
• Est. completion date: February 2014

Study information

• Verified date: November 2015
• Source: University of Aberdeen
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

Up to half of all patients with clinical features of heart failure are found to have normal heart pumping function. Recently the investigators have shown that a drug called perhexiline markedly improved exercise capacity and symptoms in patients with heart failure associated with impaired cardiac pump function. In this proposal the investigators will assess whether perhexiline has beneficial effects in patients with heart failure and a normal heart pumping function.

Description:

Up to 50% of patients with symptoms of heart failure have a preserved left ventricular ejection fraction (HFpEF syndrome). Current therapy for systolic heart failure is targeted at inducing vasodilation and counteracting neuro-endocrine activation. There is a lack of a corresponding evidence base for the treatment of HEpEF. We have previously shown that perhexiline, an agent that increases the efficiency of energy production by shifting substrate utilization from free fatty acids towards glucose, was highly effective in improving exercise capacity, symptoms and cardiac function in patients with systolic heart failure. We have also recently shown that energy deficiency plays a major role in the pathophysiology of HFpEF. In this proposal we therefore aim to investigate the effectiveness of perhexiline in 70 HFpEF patients, in a 3 month randomised, double-blind, controlled trial. An interim analysis is planned after 20 patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: February 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years to 90 Years

Eligibility

Inclusion Criteria:

• HFpEF will be defined as:

• Clinical features consistent with heart failure

• LVEF = 50%, with no evidence of significant valvular disease

• No hypertrophic cardiomyopathy, and no evidence of pericardial constriction

• Peak VO2 < 80% predicted, with RER>1 and with a pattern of gas exchange on metabolic exercise testing indicating a cardiac cause for limitation)

• Patients recruited will be in sinus rhythm

Exclusion Criteria:

• BMI >35

• Objective evidence of lung disease on formal lung function testing

• Reversible myocardial ischaemia on contrast-enhanced myocardial stress Echocardiography, and no evidence of exercise-induced mitral regurgitation (>2+)

• Impaired hepatic function; known hypersensitivity to perhexiline

Study Design

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

Related Conditions & MeSH terms

• Diastolic Heart Failure
• Heart Failure
• Heart Failure, Diastolic

Intervention

Drug:
• Perhexiline
100mg o bd for 3 months
• Placebo
Placebo one tablet bd for 3 months

Locations

Country	Name	City	State
United Kingdom	University of Aberdeen	Aberdeen

Sponsors (1)

Lead Sponsor	Collaborator
University of Aberdeen

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Peak oxygen consumption (Vo2max)		3 months	No
Secondary	Symptomatic Status (Modified Minnesota Living with Heart Failure Questionnaire)		3 Months	No
Secondary	Resting myocardial energetics by cardiac MR spectroscopy (MRS)		3 months	No
Secondary	Resting and exercise diastolic function (nuclear studies)		3 months	No
Secondary	Indirect measures of resting LVEDP (tissue Doppler E/Ea)		3 months	No
Secondary	Global LV Ejection Fraction (MRI / nuclear studies)		3 months	No