The Efficacy and Mechanism of Trientine in Patients With Hypertrophic Cardiomyopathy

NCT ID: NCT04706429

Last Updated: 2025-09-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 154 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-01
• Study Completion Date: 2024-07-30

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.

Detailed Description

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.

Conditions

Hypertrophic Cardiomyopathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Trientine

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).

Group Type: ACTIVE_COMPARATOR

Trientine

Intervention Type: DRUG

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

Placebo

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).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

Trientine

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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Other Intervention Names

Cufence

Eligibility Criteria

Inclusion Criteria

1. Written informed consent.

2. Age 18-75 inclusive.

3. 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).

4. New York Heart Association class I, II or III at the most recent clinical assessment performed prior to the baseline visit.

Exclusion Criteria

1. Previous or planned septal reduction therapy.

2. Previously documented myocardial infarction or severe coronary artery disease.

3. Uncontrolled hypertension, defined as a systolic blood pressure of >180mmHg or a diastolic blood pressure of > 100mmHg at Visit 1.

4. 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.

5. Previously documented persistent atrial fibrillation.

6. Anaemia, defined as haemoglobin being below the local site normal reference range, at Visit 1.

7. Iron deficiency, defined as serum iron being below the local site normal reference range, at Visit 1.

8. Copper deficiency, defined as serum copper being below the normal reference range, at Visit 1.

9. Pacemaker or implantable cardioverter defibrillator.

10. Known severe valvular heart disease, as demonstrated on the most recent heart imaging performed prior to the baseline visit.

11. Previously documented other cardiomyopathic cause of myocardial hypertrophy (e.g. amyloidosis, Fabry disease, mitochondrial disease).

12. History of hypersensitivity to any of the components of the investigational medicinal product (IMP).

13. Known contraindication to MRI scanning.

14. 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.

15. 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute for Health Research, United Kingdom

OTHER_GOV

Sponsor Role: collaborator

University of Manchester

OTHER

Sponsor Role: collaborator

University of Liverpool

OTHER

Sponsor Role: collaborator

Univar BV

INDUSTRY

Sponsor Role: collaborator

University of Oxford

OTHER

Sponsor Role: collaborator

Manchester University NHS Foundation Trust

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chris Miller

Role: PRINCIPAL_INVESTIGATOR

Manchester University NHS Foundation Trust

Locations

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

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

Countries

United Kingdom

References

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.

Reference Type: DERIVED

PMID: 37137675 (View on PubMed)

Other Identifiers

2020-002242-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ISRCTN57145331

Identifier Type: REGISTRY

Identifier Source: secondary_id

NIHR127575

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

B00844

Identifier Type: -

Identifier Source: org_study_id