Perhexiline Therapy in Heart Failure With Preserved Ejection Fraction Syndrome

Phase 2

Completed

• Conditions: Diastolic Heart Failure
• Interventions: Drug: Placebo; Drug: Perhexiline

• Registration Number: NCT00839228
• Lead Sponsor: University of Aberdeen

Brief 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.

Detailed 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.

Study Timeline

• Study First Submitted: 2009-02-06
• Study First Submitted QC: 2009-02-06
• Study First Posted: 2009-02-09
• Study Start: 2009-03
• Primary Completion: 2014-02
• Study Completion: 2014-02
• Status Verified: 2015-11
• Last Update Submitted: 2015-11-04
• Last Update Posted: 2015-11-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 70

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo one tablet bd for 3 months
Perhexiline	Perhexiline	perhexiline 100mg o bd for 3 months

Primary Outcome Measures

Name	Time	Method
Change in Peak oxygen consumption (Vo2max)	3 months

Secondary Outcome Measures

Name	Time	Method
Symptomatic Status (Modified Minnesota Living with Heart Failure Questionnaire)	3 Months
Resting myocardial energetics by cardiac MR spectroscopy (MRS)	3 months
Resting and exercise diastolic function (nuclear studies)	3 months
Indirect measures of resting LVEDP (tissue Doppler E/Ea)	3 months
Global LV Ejection Fraction (MRI / nuclear studies)	3 months

Trial Locations

Locations (1)

University of Aberdeen; 🇬🇧 Aberdeen, United Kingdom