Inoperable chronic thromboembolic pulmonary hypertension (CTEPH) MedDRA version: 8.1 Level: LLT Classification code 10037436 Term: Pulmonary thromboembolism
Conditions
Sponsors
Actelion Pharmaceuticals Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: · Symptomatic pulmonary hypertension in modified NYHA functional class II to IV due to CTEPH as demonstrated by ventilation/perfusion lung scanning and pulmonary angiography. · CTEPH judged inoperable because of peripheral localization of thrombotic material or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy (PEA) with no evidence of recurrent thromboembolism and not amenable to repeated surgery. · 6-minute walk test (6MWT) distance = 25 mmHg ii. Pulmonary capillary wedge pressure (PCWP) = 300 dyn.sec/cm5 For patients who underwent PEA, hemodynamic evaluation must have been performed more than 6 months after PEA. For all patients, hemodynamic evaluation must have been performed with the 3 months immediately preceding inclusion. · Men or women >= 18 and ==65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: · Other forms of pulmonary hypertension including pulmonary hypertension related to sickle cell disease. · Obstructive lung disease: FEV1/FVC 3 times the upper limit of normal ranges. · Hemoglobin concentration < 75% the lower limit of normal ranges. · Pregnancy or breast-feeding. . Systolic blood pressure (BP) < 85 mmHg. · Treatment or planned treatment with another investigational drug and/or pulmonary angioplasty within 3 months prior to randomization. · Treatment with an endothelin receptor antagonist, a phosphodiesterase inhibitor, L-arginine or with prostanoids (excluding acute administration during a catheterization procedure to test vascular reactivity) within 3 months prior to randomization. · Treatment for pulmonary hypertension within 1 month prior to randomization, excluding calcium channel blockers if present for at least 1 month before randomization. · Treatment with calcineurin-inhibitors (e.g., cyclosporine A and tacrolimus), sirolimus, fluconazole, glibenclamide (glyburide) within 1 week prior to randomization. · Known hypersensitivity to bosentan or any of the excipients
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate that bosentan improves exercise capacity and/or pulmonary vascular resistance (PVR) in patients with inoperable CTEPH.;Secondary Objective: · To evaluate the effect of bosentan on the time to clinical worsening, NYHA class and cardiac hemodynamics in patients with inoperable CTEPH. . To evaluate the safety and tolerability of bosentan in this patient population.;Primary end point(s): There are two Co-Primary Endpoints: 1. Change from baseline to Week 16 in 6MWT distance. A mean difference from placebo of at least 35 m is considered clinically relevant. This parameter is expected to be normally distributed with a standard deviation of 65 m. 2. PVR at rest at Week 16 expressed as percent of the baseline value. A geometric mean in the active group showing a reduction of at least 20% when compared to the placebo geometric mean is considered clinically relevant. The natural logarithm of this parameter is expected to be normally distributed with a standard deviation of 0.280. | — |
Countries
Germany, Italy, Spain, United Kingdom
Outcome results
None listed