Metabolic manipulation in chronic heart failure: study protocol for a randomised controlled trial

Roger M Beadle, Lynne K Williams, Khaild Abozguia, Kiran Patel, Francisco Leyva Leon, Zaheer Yousef, Anton Wagenmakers, Michael P Frenneaux, Roger M Beadle, Lynne K Williams, Khaild Abozguia, Kiran Patel, Francisco Leyva Leon, Zaheer Yousef, Anton Wagenmakers, Michael P Frenneaux

Abstract

Background: Heart failure is a major cause of morbidity and mortality in society. Current medical therapy centres on neurohormonal modulation with angiotensin converting enzyme inhibitors and β-blockers. There is growing evidence for the use of metabolic manipulating agents as adjunctive therapy in patients with heart failure. We aim to determine the effect of perhexiline on cardiac energetics and alterations in substrate utilisation in patients with non-ischaemic dilated cardiomyopathy.

Methods: A multi-centre, prospective, randomised double-blind, placebo-controlled trial of 50 subjects with non-ischaemic dilated cardiomyopathy recruited from University Hospital Birmingham NHS Foundation Trust and Cardiff and Vale NHS Trust. Baseline investigations include magnetic resonance spectroscopy to assess cardiac energetic status, echocardiography to assess left ventricular function and assessment of symptomatic status. Subjects are then randomised to receive 200 mg perhexiline maleate or placebo daily for 4 weeks with serum drug level monitoring. All baseline investigations will be repeated at the end of the treatment period. A subgroup of patients will undergo invasive investigations with right and left heart catheterisation to calculate respiratory quotient, and mechanical efficiency. The primary endpoint is an improvement in the phosphocreatine to adenosine triphosphate ratio at 4 weeks. Secondary end points are: i) respiratory quotient; ii) mechanical efficiency; iii) change in left ventricular (LV) function.

Trial registration: ClinicalTrials.gov: NCT00841139 ISRCTN: ISRCTN72887836.

Figures

Figure 1
Figure 1
Summary of study timeline. Following baseline investigations, 50 patients will be randomised to recieve 200 mg of perhexiline or matched placebo for one month. At one month all baseline tests will be repeated and a subgroup will undergo cardiac catheterisation.

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