Effect of Ivabradine on Exercise Capacity After Heart Transplantation

Cardiac Allograft Vasculopathy Clinical Trial

— VANISH-CAV  

Official title:

The Effect of Ivabradine Treatment on Exercise Capacity in Patients With Cardiac Allograft Vasculopathy After Heart Transplantation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03405831
• Other study ID #: RH-HJE-LN-01
• Status: Recruiting
• Phase: Phase 4
• Start date: April 17, 2018
• Est. completion date: December 2019

Study information

• Verified date: March 2019
• Source: Rigshospitalet, Denmark
• Contact: Finn Gustafsson, MD PhD DMSc
• Phone: +45 35459743
• Email: finng[@]dadlnet.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 35
• Est. completion date: December 2019
• Est. primary completion date: December 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Cardiac Allograft Vasculopathy
• Transplanted Heart Complication
• Vascular Diseases

Intervention

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

Locations

Country	Name	City	State
Denmark	Department of Cardiology, Copenhagen University Hospital, Rigshospitalet	Copenhagen

Sponsors (3)

Lead Sponsor	Collaborator
Finn Gustafsson	Danish Heart Foundation, Rigshospitalet, Denmark

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Coronary vessel characterization	Substudy objective: To characterize coronary vessels in CAV using new imaging modalities and relating them to functional parameters of cardiac function. Modalities performed at baseline: Intravascular ultrasound (IVUS)/Near-infrared spectroscopy (NIRS), optical coherence tomography (OCT), 82-Rubudium positron emission tomography (PET) scan	Substudy objective is only evaluated at baseline
Primary	?VO2max	The change in VO2max (?VO2max) (mL/kg/min) from baseline to 12 weeks follow-up. The peak oxygen uptake (VO2max) reflects the maximal ability of a person to take in, transport and use oxygen, and it defines the functional aerobic capacity. It is used to provide an overall assessment of exercise capacity.	The VO2max is assessed at baseline and 12 weeks follow-up.
Secondary	?HRrest	Change in resting HR (beats/min) from baseline to 12 weeks follow-up	12 weeks
Secondary	?HRreserve	Change in HR reserve (beats/min) from baseline to 12 weeks follow-up	12 weeks
Secondary	?LVmass	Change in left ventricular (LV) mass (g) evaluated by cardiac MRI from baseline to 12 weeks follow-up	12 weeks
Secondary	?LVEF	Change in left ventricular ejection fraction (LVEF) (%) evaluated by cardiac MRI from baseline to 12 weeks follow-up	12 weeks
Secondary	?mitral deceleration time	Change in mitral decelaration time (ms) evaluated by echocardiography from baseline to 12 weeks follow-up	12 weeks
Secondary	?E/é	Change in E/é evaluated by echocardiography from baseline to 12 weeks follow-up	12 weeks
Secondary	?E/A ratio	Change in E/A ratio evaluated by echocardiography from baseline to 12 weeks follow-up	12 weeks
Secondary	?isovolumetric relaxation time	Change in isovolumetric relaxation time (ms) evaluated by echocardiography from baseline to 12 weeks follow-up	12 weeks
Secondary	?transmitral flow rate	Change in transmitral flow rate (volume/min) evaluated by cardiac MRI from baseline to 12 weeks follow-up	12 weeks
Secondary	?pulmonary venous flow	Change in pulmonary venous flow (volume/min) evaluated by cardiac MRI from baseline to 12 weeks follow-up	12 weeks
Secondary	?LVEDV	Change in LVEDV (left ventricular end diastolic volume) (ml) evaluated by cardiac MRI from baseline to 12 weeks follow-up	12 weeks
Secondary	?LVESV	Change in LVESV (left ventricular end systolic volume) (ml) evaluated by cardiac MRI from baseline to 12 weeks follow-up	12 weeks
Secondary	?LV peak filling rate	Change in left ventricular (LV) peak filling rate (volume/min) evaluated by cardiac MRI from baseline to 12 weeks follow-up	12 weeks
Secondary	?time to peak filling	Change in time to peak filling (sec) evaluated by cardiac MRI from baseline to 12 weeks follow-up	12 weeks
Secondary	?QOL KCCQ	Change in QOL score evaluated by Kansas City Cardiomyopathy Questionnaire from baseline to 12 weeks follow-up	12 weeks
Secondary	?QOL EQ-5D-5L	Change in QOL score evaluated by EQ-5D-5L questionnaire from baseline to 12 weeks follow-up	12 weeks