Repurposing Valsartan May Protect Against Pulmonary Hypertension
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Six-minute walk distance
研究概览
简要总结
This is a Phase 2, single-center, randomized placebo controlled trial of valsartan (an angiotensin receptor blocker) in adults with pulmonary arterial hypertension. The study will evaluate the safety and clinical efficacy of a 24-week course of valsartan.
详细描述
Pulmonary arterial hypertension (PAH) is one of many conditions that put stress and strain on the right side of the heart. This stress and strain can cause right heart failure. Although there are medications to treat PAH, there are currently no medications that act directly on the heart to improve right heart function. This is different than left heart failure where one of the cornerstones of treatment is medication targeted at the heart to improve left heart function.
Valsartan is a well-tolerated and inexpensive medication that is currently used to treat hypertension and left heart failure. Preliminary results suggest that valsartan may help the right heart to adapt and strengthen when stressed instead of fail; however, these results are suggestive and not definitive. A randomized controlled trial is required to evaluate the possibility that valsartan can impact right heart function.
Participants in the study will take valsartan or placebo for 24 weeks. They will have three study visits at 0, 2, 12, and 24 weeks. These visits will add 20-30 minutes to the standard clinic visits at those time points and there will be an echocardiogram at weeks 0 and 24. The visits at weeks 2 and 12 may be completed remotely for most participants. Some participants may elect to participate in exercise testing and/or right heart catheterization at weeks 0 and 24; however, this is not required to participate in the trial.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, age 18 to 80
- •WHO Group 1 Pulmonary Arterial Hypertension
- •NYHA Functional Class II, III, or IV at screening (Appendix 2 for Functional Class Decision Aid)
- •Right heart catheterization within five years demonstrating a mean pulmonary arterial pressure of ≥25 mmHg, occlusion pressure of ≤15 mmHg, and resistance ≥ 3 wood units
- •Participants with a right heart catheterization within five years demonstrating a mean pulmonary arterial pressure of ≥ 25 mmHg and occlusion pressure of 15 - 20 mmHg will be considered for inclusion if the pulmonary vascular resistance ≥ 9 wood units and they are being treated with pulmonary arterial hypertension specific therapy
- •Able to walk with/without a walking aid for a distance of at least 50 meters
排除标准
- •Pregnant or lactating
- •Non-group 1 pulmonary hypertension or veno-occlusive disease
- •History of interstitial lung disease, unless subject has collagen vascular disease and has pulmonary function testing conducted within 12 months demonstrating a total lung capacity or vital capacity of ≥ 60 %
- •Has received or will receive an investigational drug, device, or study within 30 days or during the course of study
- •ACE-inhibitor, ARB or ARNI use within 30 days of randomization.
- •Left sided myocardial disease as evidenced by left ventricular ejection fraction < 40%
- •Any other clinically significant illness or abnormal laboratory values (measured during the Screening period) that, in the opinion of the Investigator, might put the subject at risk of harm during the study or might adversely affect the interpretation of the study data
- •Anticipated survival less than 1 year due to concomitant disease
- •Allergy or angioedema with ACE-inhibitor use
- •Potassium >5mEq/L or sCr >2mg/dL at screening
- •SBP <90mmHg at screening
研究组 & 干预措施
Placebo
Placebo capsule taken twice daily for 24 weeks.
干预措施: Placebo (Drug)
Valsartan
Valsartan 40mg capsule taken twice daily for 24 weeks.
干预措施: Valsartan 40 mg (Drug)
结局指标
主要结局
Six-minute walk distance
时间窗: 0 to 24 weeks
To determine whether valsartan increases six-minute walk distance at 24 weeks in men and women with pulmonary arterial hypertension.
次要结局
- Change in health related quality of life (emPHasis-10 questionnaire)(0 to 24 weeks)
- Change in BNP(0 to 24 weeks)
- Change in New York Heart Association (NYHA) functional class(0 to 24 weeks)
- Change in right ventricular morphology by echocardiogram (tricuspid annular plane systolic excursion(TAPSE))(0 to 24 weeks)
- Frequency of escalation for PAH focused care (increased diuretics, escalating doses of pulmonary vasodilators, and/or adding additional pulmonary vasodilators)(0 to 24 weeks)
- Change in right ventricular morphology by echocardiogram (right ventricular dilation)(0 to 24 weeks)
研究者
Peter Leary
Associate Professor, School of Medicine
University of Washington