Exclusion criteria
myocardial infarction, arrhythmia, Anaemia, HCM, myocardial hypertrophy, amyloidosis, Fabry disease, hypersensitivity, coronary artery disease
UNCONTROLLED HYPERTENSION, MYOCARDIAL INFARCTION, ARRHYTHMIA, ANAEMIA, VALVULAR HEART DISEASE, PERSISTENT ATRIAL FIBRILLATION, RECRUITMENT, HYPERTROPHIC CARDIOMYOPATHY, ADVERSE EVENT, AMYLOIDOSIS, FABRY DISEASE, HYPERTROPHIC CARDIOMYOPATHY, REGRESSION, BLOOD, HEART, LV HYPERTROPHY, HYPERSENSITIVITY, CORONARY ARTERY DISEASE
Previous or planned septal reduction therapy.Previously documented myocardial infarction or severe coronary artery disease.Uncontrolled hypertension, defined as a systolic blood pressure of >180 mm Hg or a diastolic blood pressure of >100 mm Hg at visit 1.Known LV EF of <50%, as measured on the most recent CMR scan performed prior to the baseline visit. If CMR has not been performed previously, the most recent echocardiogram performed prior to the baseline visit should be used.Previously documented persistent atrial fibrillation.Anaemia, defined as haemoglobin being below the local site normal reference range, at visit 1.Iron deficiency, defined as serum iron being below the local site normal reference range, at visit 1.Copper deficiency, defined as serum copper being below the normal reference range, at visit 1.Pacemaker or implantable cardioverter defibrillator.Known severe valvular heart disease, as demonstrated on the most recent heart imaging performed prior to the baseline visit.Previously documented other cardiomyopathic cause of myocardial hypertrophy (eg, amyloidosis, Fabry disease and mitochondrial disease).History of hypersensitivity to any of the components of the investigational medicinal product.Known contraindication to MRI scanning.Pregnancy, lactation or planning pregnancy. Women of childbearing capacity are required to have a negative serum pregnancy test before treatment, must agree to pregnancy tests at study visits as defined in the protocol and must agree to maintain highly effective contraception as defined in the protocol.Any medical condition, which in the opinion of the investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study.*The original upper age limit was 70 years, but this was increased to 75 years in a protocol amendment in order to aid recruitment. See CMR, cardiovascular magnetic resonance; EF, ejection fraction; ESC, European Society of Cardiology; HCM, hypertrophic cardiomyopathy; LV, left ventricular; NYHA, New York Heart Association; TEMPEST, The Efficacy and Mechanism of Trientine in Patients with Hypertrophic Cardiomyopathy.
Visit scheduleOther abbreviations as per *Visit 2 (randomisation) should take place within 28 days (4 weeks) of visit 1.†Optional procedures performed at the investigator’s discretion‡Urine test (efficacy): early morning urine collection for urine copper.§Applies to females of childbearing capacity only. A serum pregnancy test will be performed at visit 1. Urine pregnancy tests will be performed at subsequent visits (serum testing may be performed if timely urine testing is not available).¶At visit 2, female participants of childbearing capacity will be asked if there is a chance that they could have become pregnant since visit 1. If the participant confirms that there is a chance, then a urine pregnancy test will be performed.**Blood tests (safety): blood count, renal function, serum iron, serum copper and serum caeruloplasmin.††Haematocrit blood test (used as part of the CMR measurements)‡‡May be performed at visit 1 or visit 2 but must be done before randomisation.AE, adverse event; CMR, cardiovascular magnetic resonance; eCRF, electronic case report form; IMP, investigational medicinal product; SAE, serious adverse event.TEMPEST trial objectives and outcome measuresIncreases urinary copper excretion.Improves exercise capacity.Reduces arrhythmia burden.Reduces cardiomyocyte injury.Improves LV contractile function.Improves left atrial structure and function.Trientine, compared with placebo, leads to cellular or extracellular mass regression.Trientine, compared with placebo, leads to an improvement in myocardial energetics.LV hypertrophy regression is mediated by cellular regression, extracellular regression or improved myocardial energetics, which are in turn determined by copper excretion.CMR, cardiovascular magnetic resonance; LV, left ventricular; PCr:ATP, phosphocreatine to ATP; TEMPEST is conducted by the research team, in conjunction with Liverpool Clinical Trials Centre, a UK Clinical Research Collaboration fully registered clinical trials unit. The sponsor is Manchester University NHS Foundation Trust. The trial is funded by the Efficacy and Mechanism Evaluation Programme, a Medical Research Council and UK National Institute for Health and Care Research (NIHR) partnership (project reference NIHR127575). The funder had no role in trial design other than through their external peer review processes, and were not involved in the preparation, drafting or editing of this article. Univar Solutions B.V. has gifted the investigational medicinal product (IMP). Univar Solutions B.V. have had no role in trial design, and were not involved in the preparation, drafting or editing of this article. Univar Solutions B.V. conducted a factual accuracy check of this article, but any decisions to incorporate comments were made solely at the discretion of the authors. All authors reviewed and approved the manuscript and assume full responsibility for its accuracy.A Trial Steering Committee provides overall supervision for the trial and provides advice through its independent Chairman. An independent data and safety monitoring committee is responsible for reviewing and assessing recruitment, interim monitoring of safety and effectiveness, trial conduct and external data, and submits periodic reports to the Trial Steering Committee. Further details are available in the 