Beta 3 Agonist Treatment in Heart Failure-2
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- Change in invasive hemodynamics assesses by right heart catherization
研究概览
简要总结
Objective: The objective of the study is to assess the structural and functional cardiac effects of treatment with the beta 3 AR agonist Mirabegron in patients with moderate to severe chronic heart failure (LVEF<35%, NYHA III-IV).
The study is a randomized, placebo-controlled, double-blinded trial in two phases with two hypotheses:
Chronic study - study A: Long-term treatment (3 months) with the β3 adrenergic receptor agonist Mirabegron is beneficial in patients with moderate to severe human heart failure
Invasive study - Study B: Administration of Mirabegron in patients with heart failure leads to an immediate increase in cardiac output at a constant or reduced left ventricular filling pressure during submaximal exercise
Specific aims
- Determine safety of administration of Mirabegron to patients with moderate to severe heart failure.
- Determine if treatment with Mirabegron for 3 months induces beneficial cardiac structural remodelling in patients with moderate to severe heart failure. In an open-label follow-up to determine the effects of Mirabegron after an extended duration (a total of 12 months).
- Determine if Mirabegron improves symptoms and exercise capacity as indicated by questionnaires and 6 min walk test in patients with moderate to severe heart failure.
- Determine effects of Mirabegron on cardiac conduction, repolarisation and rhythms and arrhythmias in patients with moderate to severe heart failure.
- Determine effects of Mirabegron on circulating biomarkers in patients with moderate to severe heart failure.
- Determine the immediate and short term haemodynamic effects of Mirabron as measured by CT and invasively.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Stable heart failure NYHA class III-IV on ischemic or non-ischemic basis
- •Left ventricular ejection fraction (LVEF) < 35% as assessed by cardiac CT
- •NT proBNP > 1000 pg/ml
- •On optimised evidence-based pharmacological HF treatment stable ≥2 weeks with no current plan for changing HF therapy. The therapy must include a beta-blocker.
- •No change in diuretics ≤1 week
- •No admittances to hospital for treatment with intravenously administered positive inotropic agents ≤ 4 weeks.
排除标准
- •Acute myocardial infarction (AMI) or revascularisation < 3 month ago
- •Uncorrected significant primary obstructive valve disease
- •Planned major surgery including cardiac revascularisation
- •Hemodynamically significant obstructive cardiomyopathy
- •Acute myocarditis or constrictive pericarditis
- •Clinically significant hepatic (transaminases or bilirubin x 3 above upper reference level) or renal (GFR< 30 ml/min/1,73 m2) diseases
- •Heart failure due to uncorrected thyroid disease
- •Cardiac mechanical support
- •< 6 months after CRT
- •Uncontrolled hypotension (defined as symptomatic systolic blood pressure < 80 mmHg) - or hypertension (defined as systolic at 180 mmHg or above and/or diastolic blood pressure at 110 mmHg or below)
- •Unable to give informed consent
- •Reduced compliance
- •All women of child bearing potential will be required to use adequate contraception
- •Pregnant or lactating women
- •Treatment with a tricyclic antidepressant or CYP2D6 substrates other than beta-blockers or treatment with digoxin.
- •Known allergy to iodine containing contrast
- •Estimated GFR < 30 ml/min/1.73 m2
- •Congenital or drug induced QT prolongation
研究组 & 干预措施
Mirabegron
Active treatment arm (mirabegron)
干预措施: Mirabegron (Drug)
Placebo
Placebo
干预措施: Mirabegron (Drug)
结局指标
主要结局
Change in invasive hemodynamics assesses by right heart catherization
时间窗: At 3 hours and at 1 week
Study B is explorative assessing the effect on invasive parameters including cardiac output, pulmonary wedge pressure and pulmonary and systemic vascular resistance.
Increase in left ventricular ejection fraction as measured by computed tomography
时间窗: 3 months
Study A
次要结局
未报告次要终点
研究者
Henning Bundgaard
Professor
Rigshospitalet, Denmark