Perhexiline Therapy in Heart Failure With Preserved Ejection Fraction Syndrome

• ClinicalTrials.gov Identifier: NCT00839228
• Recruitment Status: Completed
• First Posted: February 9, 2009
• Last Update Posted: November 5, 2015
• Sponsor: University of Aberdeen
• Information provided by (Responsible Party): University of Aberdeen

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Diastolic Heart Failure	Drug: Perhexiline; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Randomised Double Blind Placebo Controlled Trial of Perhexiline in Heart Failure With Preserved Ejection Fraction Syndrome (HFpEF)
• Study Start Date: March 2009
• Actual Primary Completion Date: February 2014
• Actual Study Completion Date: February 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: Perhexiline; perhexiline 100mg o bd for 3 months	Drug: Perhexiline; 100mg o bd for 3 months; Other Name: Pexsig
Placebo Comparator: Placebo; Placebo one tablet bd for 3 months	Drug: Placebo; Placebo one tablet bd for 3 months; Other Name: Starch Placebo

Outcome Measures

Primary Outcome Measures :

1. Change in Peak oxygen consumption (Vo2max) [ Time Frame: 3 months ]

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 16 Years to 90 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United Kingdom

University of Aberdeen

Aberdeen, United Kingdom, AB25 2ZD

Sponsors and Collaborators

University of Aberdeen

Investigators

• Principal Investigator: Michael P Frenneaux, MBBS MD; University of Aberdeen

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Singh S, Beadle R, Cameron D, Rudd A, Bruce M, Jagpal B, Schwarz K, Brindley G, Mckiddie F, Lang C, Dawson D, Frenneaux M. Randomized double-blind placebo-controlled trial of perhexiline in heart failure with preserved ejection fraction syndrome. Future Cardiol. 2014 Nov;10(6):693-8. doi: 10.2217/fca.14.62. Erratum in: Future Cardiol. 2015 Mar;11(2):245. Nightingale, Peter [removed].

• Responsible Party: University of Aberdeen
• ClinicalTrials.gov Identifier: NCT00839228
• Other Study ID Numbers: RRK 3147; RRK 3147 ( Other Identifier: Research and Development ); MREC 08/H1207/84 ( Other Identifier: Ethics ); EudraCT 2006-001109-28 ( Registry Identifier: European Clinical Trials )
• First Posted: February 9, 2009
• Last Update Posted: November 5, 2015
• Last Verified: November 2015

Keywords provided by University of Aberdeen:

diastolic dysfunction; cardiac energetics; perhexiline; magnetic resonance spectroscopy

Additional relevant MeSH terms:

Heart Failure; Heart Failure, Diastolic; Heart Diseases; Cardiovascular Diseases; Perhexiline; Calcium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Vasodilator Agents