The Acute Effects of Dry Powder Inhaled Treprostinil on Stroke Volume Augmentation and Dead Space Ventilation in Patients With Exercise-induced Pulmonary Hypertension
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 8
- 主要终点
- Stroke volume augmentation before and after inhaled treprostinil
研究概览
简要总结
This study aims to investigate therapies for exercise induced pulmonary hypertension (EiPH). This is a condition that effects the blood vessels in the lungs and causes shortness of breath with activity. Currently, there are very limited treatment options for this condition. Inhaled treprostinil, also known as Tyvaso, is a medication used to treat other forms of lung disease and is safe and well tolerated. This study will measure the ability of Tyvaso to improve symptoms related to EiPH and improve performance on exercise testing.
详细描述
Exercise-induced pulmonary hypertension (EiPH) is defined by the presence of normal resting pulmonary hemodynamics with an abnormal elevation in mean pulmonary artery pressure (mPAP) for a given cardiac output with exercise. EiPH is typically characterized by exertional dyspnea, with the absence of other features of resting pulmonary arterial hypertension (PAH) such as elevated right atrial pressure at rest or lower extremity peripheral edema. Since patients with EiPH have normal resting echocardiograms, the disease is often underdiagnosed. Exercise right-heart catheterization remains the gold standard in diagnosing EiPH.
Aside from subjective markers of clinical improvement with therapy, assessment for physiological improvement is challenging since most measures of PAH severity, including echocardiograms, biomarkers and risk calculators, are normal at baseline in this population with EiPH. The investigators have pioneered the use of non-invasive cardiopulmonary exercise testing (CPET) to assess patients with cardiopulmonary limitations during exercise. Changes in oxygen pulse (O2 pulse) during exercise on CPET have previously been validated as an accurate predictor of stroke volume augmentation, which is an important physiological adaptation to exercise, and may serve as an objective marker of improvement in patients with EiPH.
While the guidelines agree that EiPH is real and under-diagnosed, there is no consensus on the management since these patients have not been included in high-quality clinical trials for PAH treatment. Given the lack of treatment guidelines for EiPH, many providers use PAH-targeted therapy off-label in EiPH. Specifically, generic phosphodiesterase-5 inhibitors are the typical first line agent due to insurance barriers to accessing other therapies. Inhaled treprostinil (Tyvaso DPI) would be an ideal medication for this population. Tyvaso DPI is a convenient, inhaled medication with quick onset. The favorable pharmacokinetic profile raises the potential of this medication for dosing prior to exertion for patients with EiPH.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Provision of signed and dated informed consent form
- •Stated willingness to comply with all study procedures and availability for the duration of the study
- •Persons, aged 18 years of older
- •Established diagnosis of exercise induced pulmonary hypertension defined by the following:
- •Invasive cardiopulmonary exercise testing demonstrating a mean pulmonary artery pressure to cardiac output (P/Q slope) greater than 3 mmHg/L/min
- •Symptoms of exertional dyspnea
- •Ability to perform non-invasive cardiopulmonary exercise testing, either on upright bicycle or treadmill
- •If childbearing age, patient must agree to use of effective contraception during the trial
排除标准
- •Diagnosis of pulmonary hypertension as defined by resting mean pulmonary arterial pressure of ≥ 20 mmHg, PVR > 3
- •Severe underlying chronic lung disease (e.g. COPD, interstitial lung disease)
- •Underlying chronic left ventricular disease (e.g. heart failure with reduced ejection fraction)
- •Chronic thromboembolic disease
- •Pregnancy
- •Acute infectious symptoms including fevers within the last week
- •Inability or unwillingness to discontinue any phosphodiesterase 5 inhibitors or other off-label
- •Known allergic reactions to inhaled treprostinil
- •Inability to comply with study protocols
研究组 & 干预措施
Treatment group
Single arm, every participant will receive inhaled treprostinil
干预措施: Inhaled treprostinil (Drug)
结局指标
主要结局
Stroke volume augmentation before and after inhaled treprostinil
时间窗: 30 minutes after initial dose of inhaled treprostinil
Stroke volume augmentation is a physiologic parameter which reflects the hearts ability to respond to physiologic demands of exercise. Stroke volume can be inferred during cardiopulmonary exercise testing by calculating the O2 pulse. Oxygen uptake (VO2) and heart rate are directly measured during cardiopulmonary exercise testing. O2 pulse is calculated by dividing VO2 by heart rate. Stroke volume augmentation is the ratio of O2 pulse at baseline (at the beginning of exercise) and at anaerobic threshold. Stroke volume augmentation will be measured before and after treatment with inhaled treprostinil to assess for improvements in heart function during exercise.
次要结局
- PAH Sympact Scoring(8 weeks)
- Long term stroke volume augmentation(8 weeks)
- Dead space ventilation(30 minutes, 8 weeks)
研究者
Timothy Fernandes
Clinical Professor
University of California, San Diego