Beta Blockers in Pulmonary Arterial Hypertension (PAH) A Pilot Study of Efficacy and Safety
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Mean change in RVEF
研究概览
简要总结
Estimate the effect of chronic beta-adrenergic receptor blockade with carvedilol on RV function in patients with PAH.
Assess the safety and tolerability of chronic carvedilol therapy in patients with PAH
详细描述
This is a prospective, open label, uncontrolled, pilot study examining the safety and efficacy of beta-blocker therapy with carvedilol on RV function in stable PAH Patients with World Health Organization (WHO) functional class II or III symptoms and RV ejection fraction (EF) < 40%. Twenty-five evaluable patients will be enrolled at the University of Minnesota.
Specific Aims:
1.1 Primary Efficacy Endpoint: Adult males and females on a stable dose of an approved PAH medication will undergo cardiac magnetic resonance imaging (MRI), right heart catheterization (RHC), echocardiogram, 6-minute walk test (6-MWT), measurement of plasma NT-ProBNP and serum catecholamine, and quality of life assessment. Patients will receive carvedilol (3.25 mg/kg bid escalating to 25 mg/kg bid over 3 months). Testing is repeated at the end of the study (month 6). RVEF measured by cardiac MRI is the primary efficacy endpoint. We define a 5% increase in RVEF as a meaningful change.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects will be eligible to participate in the study if all of the following conditions exist:
- •Age > 18 years
- •WHO category 1 pulmonary arterial hypertension (Dana Point 2008)
- •WHO functional class II-III
- •RVEF by cardiac MRI < 40%
- •Mean pulmonary artery pressure > 40 mm Hg
- •Stable on PAH-specific therapy as defined by no change in PAH-specific treatment and functional class in the past 3 months. Patient can be on either mono or combination PAH-specific therapy
排除标准
- •Subjects will be excluded from participation in the study if any of the following conditions exist:
- •Significant persistent bradycardia (resting heart rate < 60 bpm) without a permanent pacemaker
- •Second or third degree AV block without a permanent pacemaker
- •Significant sinus tachycardia (resting heart rate > 100 bpm)
- •Use of anti-arrhythmic drugs
- •Hypotension defined as systolic blood pressure < 100 mmHg at the time of enrollment
- •Significant illness in the past 30 days requiring hospitalization
- •Acute decompensated right heart failure within past 30 days
- •Known allergy or intolerance to carvedilol or other β blockers
- •Cardiac index < 2 l/min/m2 or right atrial pressure > 15 mm Hg
研究组 & 干预措施
Carvedilol
Carvedilol 0-3.125 mg daily Escalating to 6.25 twice a day
干预措施: Carvedilol (Drug)
结局指标
主要结局
Mean change in RVEF
时间窗: Baseline and 6 months
1. The primary efficacy outcome is the mean change in RVEF as measured by cardiac MRI before and after 6 months of carvedilol treatment. An improvement of 5% will be considered to be clinically significant. Assessment of the RV is challenging due to its complex geometry. Cardiac MRI offers the ability to acquire 3-dimensional datasets that do not require geometric modeling. In addition to being highly reproducible40, RVEF measured by cardiac MRI can be used to identify PAH patients that are likely to have clinical worsening41. The prognostic ability of cardiac MRI-measurements of RVEF is similar to that as mean pulmonary artery pressure and exercise capacity
次要结局
- Absence of Adverse Events(6 months)