Effects of Spironolactone on Collagen Metabolism in Pulmonary Arterial Hypertension
试验速览
- 阶段
- 4 期
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Change in biomarker levels in the spironolactone treated as compared to placebo treated group.
研究概览
简要总结
The purpose of this study is to determine the effects of spironolactone on collagen markers in a large number of patients with pulmonary hypertension. In addition, safety and tolerability of spironolactone, an aldosterone receptor antagonist, in patients with pulmonary arterial hypertension, will be determined.
详细描述
Pulmonary arterial hypertension (PAH) is an orphan disease characterized by pulmonary artery hypertrophy, and resulting vascular remodeling of involved vessels, often leading to right heart failure. Accumulating evidence from vascular biology, animal models, and therapeutic drug trials suggests significant contributions of the neurohormonal milieu to the disease process, morbidity, and mortality. The renin-angiotensin-aldosterone system (RAAS) is an important neurohormonal pathway that induces collagen synthesis in the myocardium and systemic vasculature. There is paucity of data regarding the contribution of RAAS in the pathogenesis of PAH and the effects of aldosterone blockade in the amelioration of PAH. Thus, the overall goal of this proposal is to investigate the contribution of RAAS to the pathogenesis of PAH, and to explore the effects of an aldosterone blocker, spironolactone, in PAH.
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
- Triple (Participant, Care Provider, Investigator)
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
- •Age 18 years or older
- •Body weight > 40 kg
- •PAH Diagnostic Group I
- •Stable subjects with no change in PAH specific therapy within the last 4 weeks
- •No change in dose of background therapy (digoxin, diuretic) within the last 2 weeks excluding anticoagulation
排除标准
- •Unable to give informed consent
- •Hemodynamically unstable subjects
- •Pregnant or breast feeding
- •Have significant renal insufficiency (serum creatinine >2.5 mg per deciliter or required hemodialysis)
- •Have significant liver dysfunction (AST or ALT more than three times upper limit of normal)
- •Currently on aldosterone receptor blocker (spironolactone or eplerenone) or ACE inhibitor
- •PH due to left heart disease
- •Unable or unwilling to comply with study procedures
研究组 & 干预措施
Spironolactone
Drug: Spironolactone Drug: Placebo
干预措施: Spironolactone (Drug)
Placebo
Drug: Placebo Drug: Spironolactone
干预措施: Placebo (Drug)
结局指标
主要结局
Change in biomarker levels in the spironolactone treated as compared to placebo treated group.
时间窗: 16 week
50 participants will be enrolled in a 16-week study, and each subject will receive placebo or active drug in a random order. At the end of week 8, treatment arm for each subject will be blindly switched. Biomarker levels will be drawn 3 times (baseline, week 8, and week 16) during the study period for each subject.
次要结局
- Number of adverse events in patients treated with spironolactone as compared to placebo.(16 week)
- Composite end-point(16 week)
- Change in six-minute walk distance from baseline to week 8 and week 16.(16 week)
研究者
Zeenat Safdar
Associate Professor of Medicine
Baylor College of Medicine