The Combination Ambrisentan Plus Spironolactone in Pulmonary Arterial Hypertension Study (The CAPS-PAH Study)
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- Effect of Combination Ambrisentan + Spironolactone on Peak Volume of Oxygen Consumption (pVO2) and Cardiac Output
研究概览
简要总结
The purpose of this study is to find out if spironolactone added to ambrisentan for Pulmonary Arterial Hypertension (PAH) will increase exercise capacity. We also want to find out if spironolactone and ambrisentan effect the cardiac output (amount of blood the heart pumps every minute), right ventricle function and quality of life.
详细描述
A prospective, double blind, placebo-controlled clinical study involving 30 patients with World Health Organization (WHO) Group 1 pulmonary arterial hypertension being treated with ambrisentan randomized to receive placebo or spironolactone (50 mg/d) for 90 days using a cross-over trial design.
Eligible participants will be randomized to receive placebo or spironolactone (50 mg/d) for 90 days (Phase I). At the completion of Phase I, participants will undergo repeat end-point assessment followed by a 21-day drug washout period. Then, the 90 day crossover phase of the trial will occur (Phase II), in which participants randomized to placebo in Phase I will be treated with spironolactone (50 mg/d) in Phase II and vice versa. At the conclusion of Phase II, end-point measures are reassessed.
Spironolactone is a diuretic used in treatment of PAH patients. Spironolactone is usually added to medical treatment when doses of Lasix/Torsemide are increased and patients are at risk for hypokalemia.
Study procedures being done for this research study are the standard procedures performed on all PAH patients when they are in clinic for follow-up except for the Cardiopulmonary Exercise Test (CPET) with Innocor.
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
- Double (Participant, Care Provider)
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
- •Voluntarily gives informed consent to participate in the study.
- •Right heart catheterization demonstrating conventional mean pulmonary artery pressure (mPAP) >25, pulmonary vascular resistance (PVR) >3.0 Wood Units, pulmonary capillary wedge pressure (PCWP) <16 mmHg within two years of enrollment
- •Subject is 18 years of age or older at Screening.
- •Diagnosis of symptomatic idiopathic or heritable PAH, PAH associated with Connective Tissue Disease (CTD), PAH associated with repaired/unrepaired congenital systemic-to-pulmonary shunt, Portopulmonary hypertension or PAH associated with HIV infection.
- •New York Heart Association Functional Class II or III
- •Stable therapy with ambrisentan 5 or 10 mg every day for > 90 days.
- •Baseline 6-Minute Walk Distance 50-450m
排除标准
- •Substantial Primary Lung disease
- •forced expiratory volume at one second (FEV-1)/forced vital capacity (FVC) <0.6 and FEV-1 <70% predicted
- •diffusing capacity of lung for carbon monoxide (DLCO) <30% predicted
- •Pulmonary fibrosis
- •Left ventricular ejection fraction < 50%
- •Pulmonary capillary wedge pressure > 16 mm Hg
- •Aortic valve disease
- •Ischemic heart disease
- •Systemic hypotension (SBP <90 mm Hg)
- •Co-existing treatment with other endothelin receptor antagonists or prostacyclin analogues
- •New York Heart Association Functional Class IV
- •Chronic thromboembolic pulmonary hypertension
- •Known or suspected pulmonary veno-occlusive disease
- •Serum creatinine >2.0 mg/dL in women, Serum creatinine >2.5 mg/dL in men
- •Baseline serum potassium >5.0 milliequivalent (mEq)/L
- •Participation in ongoing drug/intervention-based clinical trial
- •Unable to provide consent
研究组 & 干预措施
Placebo Cardiopulmonary fitness
Placebo mimics spironolactone 50 mg and will be taken QD
干预措施: Ambrisentan plus Placebo (Drug)
AMB + Spiro, Cardiopulmonary fitness
Ambrisentan 5 or 10 mg every day (QD) Spironolactone 50 mg QD
干预措施: Ambrisentan plus Spironolactone (Drug)
结局指标
主要结局
Effect of Combination Ambrisentan + Spironolactone on Peak Volume of Oxygen Consumption (pVO2) and Cardiac Output
时间窗: Up to average of 20 min
Study the effect of combination ambrisentan (5-10 mg/d) + spironolactone (50 mg/d) on pVO2 and cardiac output. The pVO2 refers to a measure of general physical fitness measured during exercise.
次要结局
未报告次要终点
研究者
Bradley Maron, MD
Instructor in Medicine
Brigham and Women's Hospital