BHF Manchester Centre for Heart and Lung Magnetic Resonance Research, Manchester University NHS Foundation Trust, Manchester, UK.
Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
Heart. 2023 Jul 12;109(15):1175-1182. doi: 10.1136/heartjnl-2022-322271.
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.
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.
TEMPEST will determine the efficacy and mechanism of action of trientine in patients with HCM.
NCT04706429 and ISRCTN57145331.
肥厚型心肌病（HCM）的特征是左心室肥厚（LVH）、心肌纤维化、氧化应激增强和能量耗竭。未结合/松散结合的组织铜 II 离子是氧化应激的有力催化剂和抗氧化剂的抑制剂。曲恩汀是一种高度选择性的铜 II 螯合剂。在糖尿病的临床前和临床研究中，曲恩汀与 LVH 和纤维化减少、线粒体功能和能量代谢改善相关。在 HCM 患者的开放标签研究中，曲恩汀与心脏结构和功能的改善相关。
三嗪患者肥厚型心肌病疗效和机制研究（TEMPEST）是一项多中心、双盲、平行组、1:1 随机、安慰剂对照的 II 期临床试验，旨在评估曲恩汀在 HCM 患者中的疗效和作用机制。根据欧洲心脏病学会指南和纽约心脏协会 I-III 级诊断为 HCM 的患者被随机分配接受曲恩汀或匹配安慰剂治疗 52 周。主要结局是使用心血管磁共振测量的左心室（LV）质量与体表面积的比值变化。次要疗效目标将确定曲恩汀是否改善运动能力、减少心律失常负担、减少心肌细胞损伤、改善 LV 和心房功能以及降低 LV 流出道梯度。机制目标将确定这些作用是否通过细胞或细胞外质量消退和改善心肌能量学来介导。
TEMPEST 将确定曲恩汀在 HCM 患者中的疗效和作用机制。
NCT04706429 和 ISRCTN57145331。
