NCT02968901终止4 期
Prospective, Multicenter, Open-label Study Evaluating the Effects of First-line Oral Combination Therapy of Macitentan and Tadalafil in Patients With Newly Diagnosed Pulmonary Arterial Hypertension (OPTIMA).
Actelion18 个研究点 分布在 1 个国家目标入组 46 人开始时间: 2015年9月1日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 发起方
- 入组人数
- 46
- 试验地点
- 18
- 主要终点
- pulmonary vascular resistance (PVR)
研究概览
简要总结
The purpose of the study is to document the effect of first line dual oral combination therapy with macitentan 10mg and tadalafil 40mg on pulmonary vascular resistance (PVR) in treatment-naïve patients with newly diagnosed pulmonary arterial hypertension (PAH).
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Any PAH-specific drug therapy [e.g. any endothelin receptor antagonist, phosphodiesterase-5 inhibitors (PDE-5i), soluble guanylate cyclase stimulator, prostacyclin, prostacyclin analog, or prostacyclin receptor agonist] at any time prior to Day 1 (single-dose administration for vasoreactivity testing is permitted; previous iloprost used intermittently for the treatment of digital ulcers or Raynaud's phenomenon is permitted if stopped > 6 months prior to Day 1).
- •Subjects who changed the dose or discontinued calcium channel blockers within 1 week prior to Day
- •Initiation of diuretics within 1 week prior to RCH.
- •Subjects on oral diuretics in whom the dose has not been stable for at least 1 week prior to RHC.
- •Treatment with other PDE-5i for erectile dysfunction.
- •Treatment with strong inducers of 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, boceprevir, telaprevir, saquinavir, lopinavir, fosamprenavir, darunavir, tipranavir, atazanavir, nelfinavir, amprenavir, indinavir) ≤ 28 days prior to Day
- •History of priapism.
- •Significant aortic and mitral valve disease requiring a specific treatment.
- •Pericardial constriction.
- •Life-threatening arrhythmia.
- •Uncontrolled hypertension.
- •Symptomatic coronary artery disease.
- •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.
- •Acute myocardial infarction ≤ 12 weeks prior to Day
- •Known permanent atrial fibrillation.
- •Low blood pressure < 90/50 mmHg at screening or Day
- •Ongoing or planned treatment with nitrates and/or doxazosin.
- •DLCO < 40% of predicted value (eligible only if no sign of veno-occlusive disease according to adjudication committee);
- •Presence of ≥ 1 of the following signs of relevant lung disease at any time prior to Day 1:
- •FEV1/FVC < 70% and FEV1 < 65% of predicted after bronchodilator administration;
- •Total Lung Capacity (TLC) < 60% of predicted.
- •Known or suspicion of pulmonary veno-occlusive disease (PVOD).
- •Severe renal insufficiency (estimated creatinine clearance ≤ 30 mL/min/1.73m²) assessed by central laboratory at screening.
- •Ongoing or planned dialysis.
- •Documented severe hepatic impairment (with or without cirrhosis) according to National Cancer Institute organ dysfunction working group criteria, defined as total bilirubin > 3 x ULN accompanied by AST > ULN (assessed by central laboratory at screening) and/or Child-Pugh Class C.
- •Serum AST and/or ALT > 3 x ULN (assessed by central laboratory at screening).
- •Porto-pulmonary hypertension.
- •Hemoglobin < 100 g/L assessed by central laboratory at screening.
- •Hypersensitivity to any active substance or excipient of macitentan or tadalafil formulation.
- •Loss of vision in one eye because of non-arteritic anterior ischemic optic neuropathy (NAION), regardless of whether or not this episode was in connection with previous PDE-5i exposure.
- •Hereditary degenerative retinal disorders, including retinitis pigmentosa.
- •Pregnancy, breast-feeding, intention to become pregnant during the study or woman of childbearing potential not agree to use reliable method of contraception from screening up to 30 days after EOT
- •Hereditary problems of galactose intolerance, Lapp lactase deficiency, glucosegalactose malabsorption.
- •Any factor or condition likely to affect protocol compliance of the patient as judged by the investigator.
- •Treatment with another investigational drug (planned, or taken ≤ 12 weeks prior to Day 1).
- •Concomitant life-threatening disease with a life expectancy < 12 months.
研究组 & 干预措施
bitherapy
Experimental
Macitentan and tadalafil
干预措施: macitentan (Drug)
bitherapy
Experimental
Macitentan and tadalafil
干预措施: tadalafil (Drug)
结局指标
主要结局
pulmonary vascular resistance (PVR)
时间窗: 16 weeks
Change from Baseline to Week 16 in percentage of patients with clinically meaningful improvement of PVR (decrease of 30% from baseline to Week 16)
次要结局
- level NT-proBNP(Week 16)
- mean pulmonary arterial pressure (mPAP)(Week 16)
- cardiac index (CI)(Week 16)
- mixed venous oxygen saturation (Sv02)(Week 16)
- mean right atrial pressure (mRAP)(Week 16)
- 6MWD(Week 16)
- WHO functional class(Week 16)
- total pulmonary resistance (TPR)(Week 16)
- Number of treatment goals(Week 16)
研究者
研究点 (18)
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