This research study has been designed to test whether a drug called trientine dihydrochloride (also called Cufence) reduces heart muscle thickening, improves exercise capacity, improves heart function and reduces abnormal heart rhythms in patients with hypertrophic cardiomyopathy (HCM). The study is also assessing how trientine works in HCM. Participants will be prescribed either trientine or placebo, for a period of 12 months.
HCM is the most common inherited cardiovascular disorder. It is characterised by left ventricular (LV) myocardial hypertrophy and fibrosis. Patients can experience symptoms of effort intolerance, progressive heart failure and abnormal heart rhythms. There are currently no treatments that alter the natural history of HCM. Patients and the cardiovascular field have identified a "critical need" for clinical studies of drug therapies that target HCM pathophysiological mechanisms. Trientine dihydrochloride is a copper-chelating agent licensed for Wilson disease, a genetic disorder of copper excretion, in which patients exhibit a cardiac phenotype that mimics HCM. Proof of concept has been established through an MRC-funded study to suggest that use of trientine may also be beneficial in HCM.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
154
NHS Grampian
Aberdeen, United Kingdom
University Hospitals of Leicester NHS Foundation Trust
Leicester, United Kingdom
Liverpool Heart and Chester Hospital NHS Foundation Trust
Liverpool, United Kingdom
Royal Brompton and Harefield NHS Foundation Trust
London, United Kingdom
Left ventricular mass indexed to body surface area (LVMi)
Change in LVMi (g/m2), measured using CMR, from baseline to week 52.
Time frame: 12 months
Urine copper excretion
Cumulative urine copper excretion, measured using urinary copper, assessed from baseline to weeks 13, 26, 39 and 52.
Time frame: 12 months
Exercise capacity
Change in exercise capacity, measured using cardiopulmonary exercise testing (CPET), assessed from baseline to week 52.
Time frame: 12 months
Number of non-sinus supraventricular heart beats, presence and amount of atrial fibrillation, number of ventricular-origin beats and presence and amount of non-sustained ventricular tachycardia
Change in number of non-sinus supraventricular heart beats, presence and amount of atrial fibrillation, number of ventricular-origin beats and presence and amount of non-sustained ventricular tachycardia, in 24 hours, measured using ambulatory heart monitoring, assessed from baseline to week 52.
Time frame: 12 months
Circulating high sensitivity troponin
Change in circulating high sensitivity troponin, assessed from baseline to week 52.
Time frame: 12 months
LV global longitudinal strain, wall thickness, mass, volumes and ejection fraction (EF)
Change in LV global longitudinal strain, wall thickness, mass, volumes and ejection fraction (EF) measured using CMR, assessed from baseline to week 52.
Time frame: 12 months
Peak left ventricular outflow
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Manchester University NHS Foundation Trust
Manchester, United Kingdom
Northumbria Healthcare NHS Foundation Trust
North Shields, United Kingdom
Oxford University Hospitals NHS Foundation Trust
Oxford, United Kingdom
Change in peak left ventricular outflow tract gradient, measured using CMR, assessed from baseline to week 52.
Time frame: 12 months
Atrial volume and function
Change in atrial volume and function, measured using CMR, assessed from baseline to week 52.
Time frame: 12 months