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Rationale and design of a randomised trial of trientine in patients with hypertrophic cardiomyopathy

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posted on 2024-05-13, 15:59 authored by John Farrant, Susanna Dodd, Carly Vaughan, Anna Reid, Matthias Schmitt, Clifford Garratt, Mohammed Akhtar, Masliza Mahmod, Stefan Neubauer, Robert M Cooper, Sanjay K Prasad, Anvesha Singh, Ladislav Valkovič, Betty Raman, Zakariye Ashkir, Dannii Clayton, Olatz Baroja, Beatriz Duran, Catherine Spowart, Emma Bedson, Josephine H Naish, Chris Harrington, Christopher A Miller
AimsHypertrophic cardiomyopathy (HCM) is characterised by left ventricular hypertrophy (LVH), myocardial fibrosis, enhanced oxidative stress and energy depletion. Unbound/loosely bound tissue copper II ions are powerful catalysts of oxidative stress and inhibitors of antioxidants. Trientine is a highly selective copper II chelator. In preclinical and clinical studies in diabetes, trientine is associated with reduced LVH and fibrosis, and improved mitochondrial function and energy metabolism. Trientine was associated with improvements in cardiac structure and function in an open-label study in patients with HCM.MethodsThe Efficacy and Mechanism of Trientine in Patients with Hypertrophic Cardiomyopathy (TEMPEST) trial is a multicentre, double-blind, parallel group, 1:1 randomised, placebo-controlled phase II trial designed to evaluate the efficacy and mechanism of action of trientine in patients with HCM. Patients with a diagnosis of HCM according to the European Society of Cardiology Guidelines and in New York Heart Association classes I–III are randomised to trientine or matching placebo for 52 weeks. Primary outcome is change in left ventricular (LV) mass indexed to body surface area, measured using cardiovascular magnetic resonance. Secondary efficacy objectives will determine whether trientine improves exercise capacity, reduces arrhythmia burden, reduces cardiomyocyte injury, improves LV and atrial function, and reduces LV outflow tract gradient. Mechanistic objectives will determine whether the effects are mediated by cellular or extracellular mass regression and improved myocardial energetics.ConclusionTEMPEST will determine the efficacy and mechanism of action of trientine in patients with HCM.Trial registration numbersNCT04706429andISRCTN57145331.

History

Author affiliation

College of Life Sciences/Cardiovascular Sciences

Version

  • VoR (Version of Record)

Published in

Heart

Volume

109

Issue

15

Pagination

1175 - 1182

Publisher

BMJ

issn

1355-6037

eissn

1468-201X

Copyright date

2023

Available date

2024-05-13

Spatial coverage

England

Language

en

Deposited by

Dr Anvesha Singh

Deposit date

2024-05-09

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