NCT02558231已完成3 期
The Efficacy and Safety of Initial Triple Versus Initial Dual Oral Combination Therapy in Patients With Newly Diagnosed Pulmonary Arterial Hypertension: A Multi-center, Double-blind, Placebo-controlled, Phase 3b Study
Actelion58 个研究点 分布在 12 个国家目标入组 247 人开始时间: 2016年5月1日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 247
- 试验地点
- 58
- 主要终点
- Change From Baseline to Week 26 in Pulmonary Vascular Resistance (PVR)
研究概览
简要总结
The objective of this clinical trial is to compare the efficacy and safety of an initial triple oral treatment regimen (macitentan, tadalafil, selexipag) versus an initial dual oral treatment regimen (macitentan, tadalafil, placebo) in newly diagnosed, treatment-naïve patients with pulmonary arterial hypertension.
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
- •Signed informed consent prior to any study-mandated procedure.
- •Male or female ≥ 18 and ≤ 75 years of age at screening.
- •Initial PAH diagnosis < 6 months prior to enrollment.
- •RHC performed between Day -28 and Day 1, meeting all the following criteria:
- •Mean pulmonary artery pressure (mPAP) ≥ 25 mmHg.
- •Pulmonary artery wedge pressure or left ventricular end-diastolic pressure ≤ 15 mmHg.
- •PVR ≥ 480 dyn•sec/cm5 (≥ 6 Wood Units).
- •Negative vasoreactivity test mandatory in idiopathic, heritable, and drug/toxin induced PAH (at this or a previous RHC).
- •Symptomatic PAH belonging to one of the following subgroups:
- •Idiopathic.
- •Heritable.
- •Drug or toxin induced.
- •Associated with one of the following: connective tissue disease; HIV infection; congenital heart disease.
- •6-minute walk distance (6MWD) ≥ 50 m at screening.
- •Women of childbearing potential must not be pregnant, must perform regular pregnancy tests, and use reliable contraception.
排除标准
- •Any PAH-specific drug therapy at any time.
- •Cardio pulmonary rehabilitation program based on exercise (planned, or started ≤ 12 weeks prior to Day 1).
- •Body mass index (BMI) > 40 kg/m2 at screening.
- •Presence of three or more of the following risk factors for heart failure with preserved ejection fraction at screening:
- •BMI > 30 kg/m
- •Diabetes mellitus of any type.
- •Essential hypertension.
- •Coronary artery disease, i.e., any of the following:
- •History of stable angina or
- •More than 50% stenosis in a coronary artery (by coronary angiography) or
- •History of myocardial infarction or
- •History of or planned coronary artery bypass grafting and/or coronary artery stenting.
- •Acute myocardial infarction ≤ 12 weeks prior to screening.
- •Stroke ≤ 12 weeks prior to screening.
- •Known permanent atrial fibrillation.
- •SBP < 90 mmHg at screening or Day
- •Ongoing or planned treatment with organic nitrates and/or doxazosin.
- •Presence of one or more of the following signs of relevant lung disease at any time up to screening:
- •Diffusing capacity of the lung for carbon monoxide (DLCO) < 40% of predicted (eligible only if no or mild interstitial lung disease on computed tomography).
- •Forced vital capacity (FVC) < 60% of predicted.
- •Forced expiratory volume in one second (FEV1) < 60% of predicted.
- •Known or suspected pulmonary veno-occlusive disease (PVOD).
- •Documented severe hepatic impairment (with or without cirrhosis) according to National Cancer Institute organ dysfunction working group criteria, defined as total bilirubin > 3 × upper limit of the normal range (ULN) accompanied by aspartate aminotransferase (AST) > ULN (assessed by central laboratory at screening); and/or Child-Pugh Class C.
- •Serum AST and/or alanine aminotransferase (ALT) > 3 × ULN (assessed by central laboratory at screening).
- •Severe renal impairment (estimated creatinine clearance ≤ 30 mL/min/1.73 m2) assessed by central laboratory at screening.
- •Ongoing or planned dialysis.
- •Hemoglobin < 100 g/L assessed by central laboratory at screening.
- •Known or suspected uncontrolled thyroid disease (hypo- or hyperthyroidism).
- •Loss of vision in one or both eyes because of non-arteritic ischemic optic neuropathy (NAION).
- •Treatment with strong inducers of cytochrome P450 3A4 (CYP3A4; e.g., carbamazepine, rifampin, rifampicin, rifabutin, rifapentin, phenobarbital, phenytoin, and St. John's wort) ≤ 28 days prior to Day
- •Treatment with strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, nefazodone, ritonavir, and saquinavir) and/or strong inhibitors of CYP2C8 (e.g., gemfibrozil) ≤ 28 days prior to Day
- •Treatment with another investigational drug (planned, or taken ≤ 12 weeks prior to Day 1).
- •Hypersensitivity to any of the 3 study treatments or any excipient of their formulations.
- •Pregnancy, breastfeeding, or intention to become pregnant during the study.
- •Concomitant life-threatening disease with a life expectancy < 12 months.
- •Alcohol abuse.
- •Any factor or condition likely to affect protocol compliance of the subject, as judged by the investigator.
研究组 & 干预措施
Triple oral combination treatment
Experimental
Macitentan, tadalafil, and selexipag
干预措施: Macitentan (Drug)
Triple oral combination treatment
Experimental
Macitentan, tadalafil, and selexipag
干预措施: Tadalafil (Drug)
Triple oral combination treatment
Experimental
Macitentan, tadalafil, and selexipag
干预措施: Selexipag (Drug)
Dual oral combination treatment
Placebo Comparator
Macitentan, tadalafil, and placebo
干预措施: Macitentan (Drug)
Dual oral combination treatment
Placebo Comparator
Macitentan, tadalafil, and placebo
干预措施: Tadalafil (Drug)
结局指标
主要结局
Change From Baseline to Week 26 in Pulmonary Vascular Resistance (PVR)
时间窗: Baseline, Week 26
Change from baseline to Week 26 in PVR was expressed as the ratio of Week 26 to baseline PVR value (Week 26 divided by baseline) using re-calculated PVR. PVR was determined by right heart catheterization (RHC). A geometric least square mean ratio of Week 26 to baseline PVR less than (\<) 1 corresponds to a reduction in PVR from baseline. Missing values were imputed using a last observation carried forward (LOCF) approach.
次要结局
- Change From Baseline to Week 26 in Mean Pulmonary Arterial Pressure (mPAP)(Baseline, Week 26)
- Change From Baseline to Week 26 in Venous Oxygen Saturation (%)(Baseline, Week 26)
- Change From Baseline to Week 26 in 6-minute Walk Distance (6MWD)(Baseline, Week 26)
- Number of Participants With Disease Progression Event(Week 26, Month 12, Month 18, Month 24, Month 30, and End of Analysis Period (up to 40 months))
- Change From Baseline to Week 26 in Total Pulmonary Resistance(Baseline, Week 26)
- Change From Baseline to Week 26 in Mean Right Atrial Pressure (mRAP)(Baseline, Week 26)
- Change From Baseline to Week 26 in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) Levels(Baseline, Week 26)
- Percentage of Participants With Absence of Worsening From Baseline to Week 26 in World Health Organization (WHO) Functional Class (FC)(Week 26)
- Change From Baseline to Week 26 in Cardiac Index(Baseline, Week 26)
研究者
研究点 (58)
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