AMBITION: A Randomised, Multicenter Study of First-Line Ambrisentan and Tadalafil Combination Therapy in Subjects With Pulmonary Arterial Hypertension (PAH)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 610
- 试验地点
- 1
- 主要终点
- Number of Participants With First Adjudicated Clinical Failure (CF) Event, Death, Hospitalisation for Worsening PAH, Disease Progression, Unsatisfactory Long-term Clinical Response, All Through FAV
研究概览
简要总结
The purpose of this study is to compare the two treatment strategies; first-line combination therapy (ambrisentan and tadalafil) versus first-line monotherapy (ambrisentan or tadalafil) in subjects with Pulmonary Arterial Hypertension. This will be assessed by time to the first clinical failure event.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must have a diagnosis of Pulmonary Arterial Hypertension (PAH) due to the following:
- •a. idiopathic or heritable PAH b. PAH associated with: i. connective tissue disease (e.g., limited scleroderma, diffuse scleroderma, mixed connective tissue disease, systemic lupus erythematosus, or overlap syndrome) ii. drugs or toxins iii. Human Immunodeficiency Virus (HIV) infection iv. congenital heart defects repaired greater than 1 year prior to screening (i.e., atrial septal defects, ventricular septal defects, and patent ductus arteriosus) NB: subjects with portopulmonary hypertension and pulmonary veno-occlusive disease are NOT eligible for the study
- •Subject must have a current diagnosis of being in World Health Organisation (WHO) Functional Class II or III.
- •Subject must meet all of the following haemodynamic criteria by means of a right heart catheterization prior to screening:
- •i. mPAP of ≥25 mmHg ii. PVR ≥ 300 dynes/sec/cm5 iii. PCWP or LVEDP of ≤12 mmHg if PVR ≥300 to <500 dyne/sec/cm5 , or PCWP/LVEDP ≤ 15 mmHg if PVR ≥500 dynes/sec/cm5
- •Subject must walk a distance of ≥125m and ≤500m at the screening visit
排除标准
- •Subject received previous PAH therapy (phosphodiesterase type 5 inhibitor (PDE5i), endothelin receptor antagonist (ERA), chronic prostanoid*) within 4 weeks prior to the screening visit (*Chronic prostanoid use is considered >7 days of treatment)
- •Subject received ERA treatment (e.g., bosentan or sitaxentan) or PDE5i treatment (e.g. Sildenafil) at any time AND discontinued due to tolerance issues other than those associated with liver function abnormalities
- •Subjects who have previously discontinued ambrisentan or tadalafil in either another clinical study or commercial product (Volibris/Letairis or Adcirca) for safety or tolerability reasons.
研究组 & 干预措施
Combination ambrisentan + tadalafil
ambrisentan + tadalafil
干预措施: ambrisentan (Drug)
Combination ambrisentan + tadalafil
ambrisentan + tadalafil
干预措施: tadalafil (Drug)
Monotherapy ambrisentan
ambrisentan
干预措施: ambrisentan (Drug)
Monotherapy tadalafil
tadalafil
干预措施: tadalafil (Drug)
结局指标
主要结局
Number of Participants With First Adjudicated Clinical Failure (CF) Event, Death, Hospitalisation for Worsening PAH, Disease Progression, Unsatisfactory Long-term Clinical Response, All Through FAV
时间窗: From Baseline up to the Final Assessment Visit (FAV) (average of 609 days)
Time to the first adjudicated CF event (death, hospitalization for worsening pulmonary arterial hypertension \[PAH\], disease progression, or unsatisfactory long-term clinical response) after initiating either first-line combination therapy with AMB and TAD or first-line monotherapy with either drug (AMB or TAD) in par. with PAH was assessed. If data was not available for some par. following a loss to follow-up, their event times were treated as censored at their last assessment time for the statistical analyses. FAV occurred approximately 4 weeks after the predicted 105th adjudicated first CF event was reached. Par. who had an FAV, and who had no adjudicated events or whose first adjudicated event occurred after their FAV, were censored at their individual FAV. Modified Intent-to-Treat (mITT) Population: all randomized par. who met the PAH diagnosis and inclusion/exclusion criteria defined in protocol amendment 2 and who also received at least one dose of investigational product (IP).
次要结局
- Percentage of Participants With a Satisfactory Clinical Response at Week 24(Baseline and Week 24)
- Percent Change From Baseline in the N-Terminal Pro-B-Type Natriuretic Peptide at Week 24(Baseline and Week 24)
- Change From Baseline in the World Health Organization Functional Class at Week 24(Baseline and Week 24)
- Change From Baseline in the 6 Minute Walk Distance Test at Week 24(Baseline and Week 24)
- Change From Baseline in Borg Dyspnea Index at Week 24(Baseline (BL) and Week 24)