The Efficacy and Mechanism of Trientine in Patients With Hypertrophic Cardiomyopathy

NCT04706429 | Completed Phase 2 DMC

• 4 other identifiers: B008442020-002242-17ISRCTN57145331NIHR127575
• Study Type: interventional
• Target: 154
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Hypertrophic Cardiomyopathy

Outcome Measures

Primary Outcomes (1)

• Left ventricular mass indexed to body surface area (LVMi)

  Change in LVMi (g/m2), measured using CMR, from baseline to week 52.

  12 months

Secondary Outcomes (7)

• Urine copper excretion

  12 months

• Exercise capacity

  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

  12 months

• Circulating high sensitivity troponin

  12 months

• LV global longitudinal strain, wall thickness, mass, volumes and ejection fraction (EF)

  12 months

Other Outcomes (5)

• LV myocardial cellular mass

  12 months

• LV myocardial extracellular mass

  12 months

• LV myocardial extracellular volume

  12 months

Study Arms (2)

Trientine

ACTIVE COMPARATOR

Trientine dihydrochloride 1200 mg per day. This shall be taken orally as two Cufence 200mg hard capsules two times per day. The IMP will be dispensed to participants every 13 weeks for the duration of the study period (52 weeks).

Drug: Trientine

Placebo

PLACEBO COMPARATOR

The placebo shall be taken orally as two capsules two times per day. This will be dispensed to participants every 13 weeks for the duration of the study period (52 weeks).

Drug: Placebo

Interventions

Trientine DRUG

Trientine dihydrochloride is a white to pale yellow crystalline hygroscopic powder.

Also known as: Cufence

Trientine

Placebo DRUG

Placebo capsule, manufactured with the exact components of the trientine capsules, without the active ingredient / investigational medicinal product.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent.
• Age 18-75 inclusive.
• Hypertrophic cardiomyopathy (HCM), as defined by the European Society of Cardiology HCM guidelines as: "a wall thickness ≥15 mm in one or more LV myocardial segments that is not explained solely by loading conditions". The same definition is applied to first-degree relatives of patients with HCM i.e. all participants are required to have a LV wall thickness ≥15 mm. Wall thickness is as measured on the most recent cardiovascular magnetic resonance (CMR) scan performed prior to the baseline visit. If CMR has not been performed previously, wall thickness measurement should be taken from the most recent echocardiogram performed prior to the baseline visit. (It is recognised that in the European Society of Cardiology guidelines a clinical diagnosis of HCM in first-degree relatives requires a wall thickness that is less than this value, however ≥15 mm is applied here in order to ensure that all participants have an unequivocal phenotype).
• New York Heart Association class I, II or III at the most recent clinical assessment performed prior to the baseline visit.

You may not qualify if:

• Previous or planned septal reduction therapy.
• Previously documented myocardial infarction or severe coronary artery disease.
• Uncontrolled hypertension, defined as a systolic blood pressure of \>180mmHg or a diastolic blood pressure of \> 100mmHg at Visit 1.
• Known LV EF \< 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 (e.g. amyloidosis, Fabry disease, mitochondrial disease).
• History of hypersensitivity to any of the components of the investigational medicinal product (IMP).
• 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 Section 8 and must agree to maintain highly effective contraception as defined in Section 8 during the study.
• 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.

Sponsors & Collaborators

• Manchester University NHS Foundation Trust: lead
• National Institute for Health Research, United Kingdom: collaborator
• University of Manchester: collaborator
• University of Liverpool: collaborator
• Univar BV: collaborator
• University of Oxford: collaborator

Study Sites (7)

NHS Grampian

Aberdeen, AB25 2ZN, United Kingdom

Location

University Hospitals of Leicester NHS Foundation Trust

Leicester, LE3 9QP, United Kingdom

Location

Liverpool Heart and Chester Hospital NHS Foundation Trust

Liverpool, L14 3PE, United Kingdom

Location

Royal Brompton and Harefield NHS Foundation Trust

London, SW3 6NP, United Kingdom

Location

Manchester University NHS Foundation Trust

Manchester, M23 9LT, United Kingdom

Location

Northumbria Healthcare NHS Foundation Trust

North Shields, NE29 8NH, United Kingdom

Location

Oxford University Hospitals NHS Foundation Trust

Oxford, OX3 9DU, United Kingdom

Location

Related Publications (1)

• Farrant J, Dodd S, Vaughan C, Reid A, Schmitt M, Garratt C, Akhtar M, Mahmod M, Neubauer S, Cooper RM, Prasad SK, Singh A, Valkovic L, Raman B, Ashkir Z, Clayton D, Baroja O, Duran B, Spowart C, Bedson E, Naish JH, Harrington C, Miller CA; TEMPEST investigators. Rationale and design of a randomised trial of trientine in patients with hypertrophic cardiomyopathy. Heart. 2023 Jul 12;109(15):1175-1182. doi: 10.1136/heartjnl-2022-322271.

  PMID: 37137675 DERIVED

MeSH Terms

Conditions

Cardiomyopathy, Hypertrophic

Interventions

Trientine

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Aortic Valve Disease; Heart Valve Diseases

Intervention Hierarchy (Ancestors)

Ethylenediamines; Diamines; Polyamines; Amines; Organic Chemicals

Study Officials

• Chris Miller

  Manchester University NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2021
• First Posted: January 12, 2021
• Study Start: December 1, 2020
• Primary Completion: April 30, 2024
• Study Completion: July 30, 2024
• Last Updated: September 29, 2025

Record last verified: 2025-09

Locations

GB (7)