Safety and Efficacy Trial Using Ambrisentan for Pulmonary Hypertension Associated With Congestive Heart Failure With Preserved Left Ventricular Ejection Fraction
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- Safety Assessment-Number of Subjects Who Are Free and Those Who Developed Clinically Significant Adverse Events (CSAEs)
研究概览
简要总结
This is a randomized study of ambrisentan that will last 16 weeks. The study will include patients with diastolic heart failure and pulmonary hypertension. Patients will be randomized (1:1) to ambrisentan or placebo. The ambrisentan or matching placebo will be started at 2.5 mg by mouth daily and increased to 5mg and then 10mg daily, if tolerated. Patients will be seen at least monthly for 16 weeks. Adverse reactions will be reviewed and the required monthly laboratory tests (liver function testing and pregnancy testing, if applicable), will be performed. Patients will also complete an exercise test (six minute walk distance) and a quality of life survey at the baseline, week 4 and week 16 visit. An echocardiogram and a right heart catheterization and left ventricular end diastolic pressure measurement will be performed at the 16 week visit. The primary end-point is safety, and secondary end-points include the catheterization results, echocardiogram results, the walk distance and the quality of life survey. The expected completion of the study is 18 months from initiation. Ambrisentan is an FDA approved drug for PAH, but not for CHF.
详细描述
Hypothesis
patients with pulmonary hypertension secondary to diastolic congestive heart failure (CHF) treated with ambrisentan for 16 weeks will have improved hemodynamics, increased exercise capacity and improved functional class with an acceptable safety profile, compared with placebo treated patients.
Objectives: to evaluate the safety and efficacy of ambrisentan treatment in patients with pulmonary hypertension due to diastolic CHF. Efficacy will be assessed by improvement in hemodynamics (PVR(Pulmonary Vascular Resistance): primary efficacy endpoint), six minute walk distance (6MWD), World Health Organization (WHO) functional class and quality of life after 16 weeks of treatment with ambrisentan. Safety of ambrisentan will be compared to placebo.
Concomitant Medication: Treatment with standard medications for CHF including diuretics and optimal blood pressure control with antihypertensive medications will be allowed throughout the study period. Diuretics adjustment will also be allowed and encouraged based on the planned diuretic management protocol. Approved medications for CHF in general are allowed as well, though it should be noted that there are no medications shown to have benefit in diastolic CHF. Patients may not be on an endothelin antagonist or sildenafil.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Catheterization
- •Elevated pulmonary arterial pressure (PA mean >25mmHg)
- •Elevated pulmonary vascular resistance (>240 dynes.cm.sec-5) or transpulmonary gradient (>12 mmHg)
- •Elevated LVEDP (>15mmHg, but ≤23 mmHg)
- •Evidence of left ventricular diastolic dysfunction: LA>4.0, LVH or diastolic dysfunction by mitral filling pattern
- •Echocardiogram: Normal or mildly reduced LV ejection fraction (greater than or equal to 40%)
- •Symptomatic chronic HF (WHO functional class II-IV)
- •Baseline walk distance 100 to 400 meters
- •Age 18 - 80 (increased from 70)
- •Maximal treatment of diastolic dysfunction as noted by the treating physicians with no change in medical therapy for one month prior to entry
排除标准
- •Use of endothelin receptor antagonist, prostacyclin or PDE-5 inhibitor within 4 weeks of enrollment
- •Exercise capacity limited by other illness (other lung disease, arthritis, mobility limitations)
- •Uncontrolled systemic hypertension
- •Uncontrolled atrial fibrillation
- •Severe valvular disease
- •Pregnant females- females of child bearing potential will need to use contraceptive agent barrier given the teratogenicity associated with ERA's
- •Uncontrolled OSA
研究组 & 干预措施
1
干预措施: Ambrisentan (Drug)
2
干预措施: Placebo (Other)
结局指标
主要结局
Safety Assessment-Number of Subjects Who Are Free and Those Who Developed Clinically Significant Adverse Events (CSAEs)
时间窗: 4 months
Freedom from clinically significant adverse events will be measure by determining the number free from CSAEs and those who developed CSAEs
Change in Pulmonary Vascular Resistance (Wood Units)
时间窗: Baseline and Four months
The primary efficacy outcome will be Pulmonary Vascular Resistance.PVR will be calculated as \[(PA mean - wedge) / Cardiac Output\]
次要结局
- Change in Functional Class(basline and 4 months)
- Change in Short Form-36 Physical Functioning(baseline 4 months)
- Change in 6 Minute Walk Distance(Baseline and Four months)