NCT03809156Unknown4 期
Upfront Riociguat and Ambrisentan Combination Therapy for Pulmonary Arterial Hypertension: A Safety and Efficacy Pilot Study
适应症
干预措施
相关药物
试验速览
- 阶段
- 4 期
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Pulmonary Vascular resistance
研究概览
简要总结
To evaluate the safety and efficacy of first-line combination therapy using riociguat with ambrisentan in patients with Pulmonary Arterial Hypertension (PAH).
详细描述
This is a prospective, multi-center, open-label, exploratory study with patients followed for a period of one year. The treatment duration period in this study begins at the initiation of ambrisentan plus riociguat and will continue for 12 months. Patients will come to clinic for a visit at month 4 and 12. Assessments will include Right Heart Catheterization, 6 Minute walk test, cardiac MRI, questionnaires and nt-Pro-BNP.
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
- •Signed informed consent prior to initiation of any study mandated procedure;
- •Males or females ≥ 18 years of age i. Women of childbearing potential must have a negative pre-treatment pregnancy test and must use reliable methods of contraception.
- •ii. Women not of childbearing potential are defined as postmenopausal (i.e., amenorrhea for at least 1 year), or documented surgically or naturally sterile.
- •Patients with symptomatic Functional Class III PAH in the following categories:
- •i. Idiopathic (IPAH) ii. Familial (FPAH) iii. Associated with connective tissue disease iv. Associated with drugs or toxins;
- •PAH diagnosed by right heart catheterization, defined as:
- •i. Mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg ii. PVR > 3 mmHg/l/min (Wood units) or > 240 dyn sec cm-5 iii. Pulmonary capillary wedge pressure (PCWP) ≤ 15 mmHg;
- •150 m ≤ 6 Minute Walk Test (6MWT) distance ≤ 480 m
排除标准
- •PAH associated with any other condition than those described in the inclusion criteria (patients with PAH associated with portal hypertension, HIV and CHD should not be included);
- •PAH associated with thyroid disorders, glycogen storage disease, Gaucher disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders and splenectomy;
- •Valvular disease with valvular lesions to be excluded by echocardiogram within 2 years prior to randomization (i.e., patients with tricuspid or pulmonary insufficiency secondary to PAH can be included);
- •Restrictive lung disease: total lung capacity (TLC) < 60% of normal predicted value;
- •Obstructive lung disease: forced expiratory volume/forced vital capacity (FEV1/FVC) < 0.5;
- •Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C;
- •Pregnancy or breast-feeding;
- •Systolic blood pressure < 95 mmHg;
- •Body weight < 40 kg;
- •Hemoglobin > 25% below the lower limit of the normal range;
- •Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 1.5 times the upper limit of normal ranges;
- •Renal insufficiency as defined by creatinine clearance < 30 mL/min or on dialysis
- •Treatment with phosphodiesterase type 5 inhibitors, any prostanoid (excluding acute administration during a catheterization procedure to test vascular reactivity) or with any other PH specific medication;
- •Treatment or planned treatment with calcineurin-inhibitors (i.e., cyclosporine A and tacrolimus), CYP2C9 and CYP3A4 inhibitors (i.e., ketoconazole, fluconazole) within 1 week of study start;
- •Treatment or planned treatment with nitrate drugs, short acting nitrate-containing medications, alpha blockers or protease inhibitors (i.e., ritonavir);
- •Known hypersensitivity to ambrisentan, riociguat or any of their excipients;
- •Patients with any contraindication to riociguat treatment or ERA treatment
- •Patients with syncope, a rapid rate of symptom progression or with high or rising nt-BNP levels in the judgment of the investigators
- •Any contraindications specified in the product monographs of either ambrisentan or riociguat, including:
- •Patients at increased risk of hypotension with concomitant or underlying conditions such as coronary artery disease, hypovolemia, severe left ventricular outflow obstruction or autonomic dysfunction; patients with resting hypotension
- •Patients with history of serious hemoptysis or patients who have previously undergone bronchial arterial embolization
- •Patients with pulmonary veno-occlusive disease
- •Ongoing participation in any interventional clinical studies.
研究组 & 干预措施
Combo Riociguat and Ambrisentan Therapy
Experimental
Riociguat Oral Product and Ambrisentan Oral Product to be given in combination to de novo (untreated) patients.
干预措施: Riociguat Oral Product (Drug)
结局指标
主要结局
Pulmonary Vascular resistance
时间窗: 4 and 12 months
Change from baseline to month 4 and month 12 in pulmonary vascular resistance (PVR) as assessed by Right Heart Catheterization.
次要结局
- Hemodynamic Variables(4 and 12 months)
- Echocardiographic parameters(4 and 12 months)
- RV function(4 and 12 months)
- NT-PRo-BNP(4 and 12 Months)
- Exercise capacity(4 and 12 months)
- Dyspnea(4 and 12 months)
- Quality of Life Assessment(4 and 12 months)
- Functional Class(4 and 12 months)
- Survival(12 months)
- Clinical worsening(12 months)
研究者
研究点 (2)
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