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Farrant, J, Dodd, S, Vaughan, C, Reid, A, Schmitt, M, Garratt, C, Akhtar, M, Mahmod, M, Neubauer, S, Cooper, RM, Prasad, SK, Singh, A, Valkovič, L, Raman, B, Ashkir, Z, Clayton, D, Baroja, O, Duran, B, Spowart, C, Bedson, E , Naish, JH, Harrington, C, Miller, CA and TEMPEST investigators, (2023) Rationale and design of a randomised trial of trientine in patients with hypertrophic cardiomyopathy. Heart (British Cardiac Society). ISSN 1355-6037
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Rationale and design of a randomised trial of trientine in patients with hypertrophic cardiomyopathy..pdf - Published Version Available under License Creative Commons Attribution. Download (1MB) | Preview |
Abstract
Aims Hypertrophic 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.
Methods The 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.
Conclusion TEMPEST will determine the efficacy and mechanism of action of trientine in patients with HCM.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TEMPEST investigators; cardiomyopathy, hypertrophic; hypertrophic cardiomyopathy; pharmacology, clinical; 1102 Cardiorespiratory Medicine and Haematology; 1103 Clinical Sciences; Cardiovascular System & Hematology |
| Subjects: | R Medicine > R Medicine (General) |
| Divisions: | Sport & Exercise Sciences |
| Publisher: | BMJ |
| SWORD Depositor: | A Symplectic |
| Date Deposited: | 19 May 2023 11:02 |
| Last Modified: | 19 May 2023 11:15 |
| DOI or ID number: | 10.1136/heartjnl-2022-322271 |
| URI: | https://researchonline.ljmu.ac.uk/id/eprint/19532 |
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