ARIES-3: A Phase 3, Long-Term, Open-Label, Multicenter Safety and Efficacy Study of Ambrisentan in Subjects With Pulmonary Hypertension
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 224
- 试验地点
- 39
- 主要终点
- Change From Baseline to Week 24 in 6 Minute Walk Distance (6MWD)
研究概览
简要总结
The primary objective of this study was to evaluate the safety and efficacy of ambrisentan in a broad population of participants with pulmonary hypertension (PH). Secondary objectives of this study were to evaluate the effects of ambrisentan on other clinical measures of pulmonary arterial hypertension (PAH), long-term treatment success, and survival.
详细描述
This study was to enroll up to 200 participants with PH due to the following etiologies: 1) PAH including idiopathic and familial PAH and PAH associated with collagen vascular disease, congenital systemic-to-pulmonary shunts (including Eisenmenger's syndrome), human immunodeficiency virus (HIV) infection, drugs and toxins, thyroid disorders, glycogen storage disease, Gaucher disease, hemoglobinopathies, and splenectomy (WHO Group 1); 2) PH associated with lung diseases and/or hypoxemia, including chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), sleep-disordered breathing, and alveolar hypoventilation disorders (WHO Group 3); 3) PH due to proximal or distal chronic thromboembolic obstruction (WHO Group 4); and 4) PH due to sarcoidosis (WHO Group 5). Participants with left heart disease or left heart failure were excluded (WHO Group 2). Participants could be receiving prostacyclin or sildenafil therapy at baseline, and participants who previously discontinued either bosentan, sitaxsentan, or both, due to liver function test abnormalities were eligible.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •18 years of age or older
- •Current diagnosis of PH associated with an acceptable etiology as outlined in the protocol, including: PH due to the following etiologies: 1) PAH including idiopathic and familial PAH and PAH associated with collagen vascular disease, congenital systemic-to-pulmonary shunts (including Eisenmenger's syndrome), human immunodeficiency virus (HIV) infection, drugs and toxins, thyroid disorders, glycogen storage disease, Gaucher disease, hemoglobinopathies, and splenectomy (WHO Group 1); 2) PH associated with lung diseases and/or hypoxemia, including chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), sleep-disordered breathing, and alveolar hypoventilation disorders (WHO Group 3); 3) PH due to proximal or distal chronic thromboembolic obstruction (WHO Group 4); and 4) PH due to sarcoidosis (WHO Group 5).
- •Stable regimen (within four weeks) of chronic prostanoid, PDE-5 inhibitor, calcium channel blocker, or 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor therapy
- •Right heart catheterization completed prior to screening must meet pre-specified criteria
- •Female participants of childbearing potential must have a negative serum pregnancy test and must agree to use a reliable double method of contraception until study completion and for at least four weeks following their final study visit.
- •Male participants must be informed of the potential risks of testicular tubular atrophy and infertility associated with taking ambrisentan and queried regarding his understanding of the potential risks as described in the Informed Consent Form.
排除标准
- •Participation in a previous clinical study with ambrisentan
- •Bosentan or sitaxsentan use within four weeks prior to the screening visit
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) lab value that is greater than 3 times the upper limit of normal at the screening visit
- •Pulmonary function tests not meeting the following pre-specified criteria: 1) mean pulmonary arterial pressure (PAP) >= 25 mm Hg; 2) PVR > 3 mm Hg/L/min; 3) pulmonary capillary wedge pressure (PCWP) or left ventricle end diastolic pressure (LVEDP) < 15 mm Hg; 4) total lung capacity (TLC) >= 70% of predicted normal for participants without ILD or >= 60% of predicted normal in participants with ILD; forced expiratory volume in 1 second (FEV1) >= 65% of predicted normal in participants without COPD or >= 50% of predicted normal in participants with COPD
- •Contraindication to treatment with endothelin receptor antagonist (ERA)
- •History of malignancies other than basal cell carcinoma of the skin or in situ carcinoma of the cervix within the past five years
- •Female participant who is pregnant or breastfeeding
研究组 & 干预措施
Ambrisentan
干预措施: Ambrisentan (Drug)
结局指标
主要结局
Change From Baseline to Week 24 in 6 Minute Walk Distance (6MWD)
时间窗: Baseline to Week 24
次要结局
- Percent Change From Baseline to Week 24 in B-type Natriuretic Peptide (BNP)(Baseline to Week 24)
- Change From Baseline to Week 24 in Borg Dyspnea Index(Baseline to Week 24)
- Change From Baseline to Week 48 in Borg Dyspnea Index(Baseline to Week 48)
- Percent Change From Baseline to Week 48 in BNP(Baseline to Week 48)
- Change From Baseline to Week 24 in WHO Functional Class(Baseline to Week 24)
- Change From Baseline to Week 48 in WHO Functional Class(Baseline to Week 48)
- Change From Baseline to Week 24 in SF-36 Health Survey Physical Functioning Scale(Baseline to Week 24)
- Change From Baseline to Week 48 in SF-36 Health Survey Physical Functioning Scale(Baseline to Week 48)
- Percent of Participants With no Clinical Worsening of Pulmonary Hypertension (PH) at Week 24(Baseline to Week 24)
- Failure-free Treatment Status(Baseline to Week 48)
- Monotherapy Treatment Status(Baseline to Week 48)
- Percent of Participants With no Clinical Worsening of PH at Week 48(Baseline to Week 48)
- Long-term Survival(Baseline to Week 48)