Effect of Ivabradine on Exercise Capacity After Heart Transplantation (VANISH-CAV)

Finn Gustafsson

Status and phase: Unknown; Phase 4

Conditions: Transplanted Heart Complication; Cardiac Allograft Vasculopathy

Treatments: Drug: Ivabradine; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT03405831

RH-HJE-LN-01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 35 estimated patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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35 participants in 2 patient groups, including a placebo group

Ivabradine

Active Comparator group

Description:

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

Treatment:

Drug: Ivabradine

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo