Effect of Ivabradine on Exercise Capacity After Heart Transplantation

NCT ID: NCT03405831

Last Updated: 2019-03-05

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-17
• Study Completion Date: 2019-12-31

Brief Summary

This study evaluates whether treatment with ivabradine compared to placebo can improve exercise capacity in long-term heart transplant recipients with cardiac allograft vasculopathy and elevated heart rate at rest.

Patients will receive treatment with either ivabradin or placebo for a period of 12 weeks.

Detailed Description

Elevated resting heart rate (HR) is a normal finding after successful heart transplantation (HTx) due to parasympathetic denervation at the operation.

Elevated resting HR is generally acknowledged as a negative predictor of outcome in heart disease. The impact in heart transplant recipients is not fully understood, however, it has been associated with increased risk of developing cardiac allograft vasculopathy (CAV) or death.

Cardiac allograft vasculopathy is a diffuse vascular disease affecting the entire coronary tree. It is the leading cause of death in patients more than 5 years after HTx and it is well known that patients with CAV have markedly reduced exercise capacity.

The association between elevated HR and CAV raises the question whether an intervention to specifically lower HR could improve symptoms and prognosis in heart transplant recipients with CAV and elevated resting HR.

Small studies have shown that HR reduction using the If channel blocker ivabradine after HTx is safe. However, none of these studies were randomized or blinded, and as such proof of any efficacy (beyond HR reduction) after HTx is non-existing. Clearly, there is a need to determine if such treatment could improve exercise capacity, graft function and prognosis after HTx.

Conditions

Cardiac Allograft Vasculopathy; Transplanted Heart Complication

Study Design

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

Study Groups

Ivabradine

Study participants in this arm will receive ivabradin 5 mg bid for a period of 12 weeks.

Group Type: ACTIVE_COMPARATOR

Ivabradine

Intervention Type: DRUG

Ivabradine, oral tablets, 5 mg, coated in gelatine capsules to ensure blinding, 1 capsule twice a day, for a period of 12 weeks

Placebo

Study participants in this arm will receive placebo bid for a period of 12 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo, gelatine capsules to ensure blinding, 1 capsule twice daily, for a period of 12 weeks

Interventions

Ivabradine

Ivabradine, oral tablets, 5 mg, coated in gelatine capsules to ensure blinding, 1 capsule twice a day, for a period of 12 weeks

Intervention Type: DRUG

Placebo

Placebo, gelatine capsules to ensure blinding, 1 capsule twice daily, for a period of 12 weeks

Intervention Type: DRUG

Other Intervention Names

Procoralan

Eligibility Criteria

Inclusion Criteria

• Patients > 1 year post heart transplantation
• CAV verified by coronary angiography or intravascular ultrasound
• Resting HR > 80 bpm
• Age > 18 years
• Signed informed consent

Women, who have not yet entered menopause (defined as no menstrual bleeding in the last 12 months), will be required to provide a negative urine human chorionic gonadotropin (hCG) before entering the study and must use a safe birth control method in the total study period.

Exclusion Criteria

• Rejection (>H1R) < 3 months
• Severe renal failure (estimated glomerular filtration rate (GFR) < 30 mL/min/1.73 m2)
• Inability or contraindication to perform a VO2 max test
• Presence of any condition that might per se influence exercise performance
• Known contraindication for treatment with ivabradine
• Hypersensitivity to the active substance or to any of the excipients of either study drug

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Danish Heart Foundation

OTHER

Sponsor Role: collaborator

Rigshospitalet, Denmark

OTHER

Sponsor Role: collaborator

Finn Gustafsson

OTHER

Sponsor Role: lead

Responsible Party

Finn Gustafsson

MD, PhD, DMSci; Professor of Cardiology; Team Leader Advanced Heart Failure, Transplantation and Mechanical Circulatory Support; Department of Cardiology; The Heart Center; Copenhagen University Hospital; Rigshospitalet

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Lærke Nelson, MD

Role: PRINCIPAL_INVESTIGATOR

Rigshospitalet, Denmark

Locations

Department of Cardiology, Copenhagen University Hospital, Rigshospitalet

Copenhagen, , Denmark

Site Status: RECRUITING

Countries

Denmark

Central Contacts

Finn Gustafsson, MD PhD DMSc

Role: CONTACT

finng@dadlnet.dk

+45 35459743

Lærke Nelson, MD

Role: CONTACT

laerke.marie.nelson@regionh.dk

+45 35459549

Facility Contacts

Finn Gustafsson, MD PhD DMSc

Role: primary

finng@dadlnet.dk

+45 3545 9743

Lærke Nelson, MD

Role: backup

laerke.marie.nelson@regionh.dk

+45 3545 9549

Other Identifiers

RH-HJE-LN-01

Identifier Type: -

Identifier Source: org_study_id