The Effect of Ivabradine Treatment on Exercise Capacity in Patients With Cardiac Allograft Vasculopathy After Heart Transplantation
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- ΔVO2max
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Ivabradine
Study participants in this arm will receive ivabradin 5 mg bid for a period of 12 weeks.
干预措施: Ivabradine (Drug)
Placebo
Study participants in this arm will receive placebo bid for a period of 12 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
ΔVO2max
时间窗: The VO2max is assessed at baseline and 12 weeks follow-up.
The change in VO2max (ΔVO2max) (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.
次要结局
- ΔQOL KCCQ(12 weeks)
- ΔQOL EQ-5D-5L(12 weeks)
- ΔHRrest(12 weeks)
- ΔHRreserve(12 weeks)
- ΔLVmass(12 weeks)
- ΔLVEF(12 weeks)
- Δmitral deceleration time(12 weeks)
- ΔE/é(12 weeks)
- ΔE/A ratio(12 weeks)
- Δisovolumetric relaxation time(12 weeks)
- Δtransmitral flow rate(12 weeks)
- Δpulmonary venous flow(12 weeks)
- ΔLVEDV(12 weeks)
- ΔLVESV(12 weeks)
- ΔLV peak filling rate(12 weeks)
- Δtime to peak filling(12 weeks)
研究者
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
Rigshospitalet, Denmark