Beta-blocker Therapy in Idiopathic Pulmonary Arterial Hypertension
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Effectivity
研究概览
简要总结
The main question of this study is: 'Is selective beta-blocker treatment safe and effective in reducing sympathetic overdrive, thereby improving RV function and remodeling in patients with iPAH?'.
In addition to the determination of RVEF, the investigators will explore how beta-blocker therapy affects sympathetic overdrive, remodeling of the RV, single beat elastance, exercise capacity and mechanical efficiency.
30 iPAH patients will be randomized to either Bisoprolol- or placebo-treatment in a double-blinded fashion. A cross-over trial design will be used to increase the power of the study and to assess long-term effects of Bisoprolol-treatment and -withdrawal. The medication will be given in an escalating dose regimen (as described in the 'farmacotherapeutisch kompas', www.fk.cvz.nl) and treatment will be monitored along the guidelines of the American Heart Association.
详细描述
This is a clinical study aimed to provide a proof of concept of the safety and efficacy of beta-blocker treatment in PAH-associated right ventricular failure.
The protocol of the proposed double blinded cross over design.
The reasons for not choosing an initial open phase 1 study, but to start directly with a placebo controlled study are:
- Although the drug is considered contraindicated in the studied patient population, it is very common for PAH patients to receive beta-blocker therapy in an uncontrolled way; without reports of serious side effects until now
- Dose titration in the study will be performed on the basis of side-effects and at this moment the investigators cannot predict the optimal dose which is both safe and efficacious. Therefore, safety assessment can only be performed in combination with the assessment of pharmaceutical effectiveness.
After obtaining informed consent, 30 idiopathic PAH patients (NYHA II-III) will be randomly assigned to either the placebo group or beta-blocker therapy. For the randomization and study blinding the investigators will use a VUMC computer based procedure in close collaboration with the VUMC pharmacy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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
- •Idiopathic PAH patients
- •Stable on PAH specific treatment defined
- •No change in PAH specific treatment in the past 6 months
- •No change in functional class in the past 6 months
- •<10 % change in 6 minute walk distance in the past 6 months
- •Functional class 2 or 3
- •In sinus rhythm
排除标准
- •History of systemic hypertension, ischaemic heart disease, valvular disease or cardiomyopathy.
- •Use of concomitant medication other than diuretics, Acenocoumarol and PAH targeted therapy
- •History of cardiac arrhythmias or the use of anti-arrhythmic drugs
- •Sick sinus syndrome
- •systolic hypotension < 90 mmHg
- •Clinically relevant sinus-bradycardia
研究组 & 干预措施
First placebo
First half year placebo, second half year bisoprolol
干预措施: Bisoprolol (Drug)
First Bisoprolol
First half year bisoprolol, second half year placebo
干预措施: Bisoprolol (Drug)
结局指标
主要结局
Effectivity
时间窗: 6 months
The primary efficacy endpoint is improvement in RV function as reflected by RVEF determined by means of cardiac MRI.
Safety
时间窗: continue
Safety of Bisoprolol treatment in iPAH patients is not taken as a primary endpoint but seen as a precondition for this study and will be closely monitored. Dose titration will be guided by possible side effects.
次要结局
- Is Bisoprolol treatment effective in reducing sympathetic overdrive?(0,6,12 months)
- Is Bisoprolol effective in reversing maladaptive remodeling of the right ventricular wall, and does Bisoprolol thereby improve the diastolic properties of the right ventricle?(0,6 and 12 months)
- Is Bisoprolol treatment effective in improving the perfusion and mechanical efficiency (oxygen consumption per joule) of the heart?(0,6,12 months)
- Is Bisoprolol effective in improving exercise capacity?(Every two weeks)
研究者
A. Vonk Noordegraaf
Prof. dr.
Amsterdam UMC, location VUmc