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Prospective, randomized, placebo-controlled, double-blind, multicenter, parallel group study to assess the efficacy, safety and tolerability of bosentan in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) - BENEFIT

Phase 1
Conditions
Inoperable chronic thromboembolic pulmonary hypertension (CTEPH)
Registration Number
EUCTR2005-001965-33-CZ
Lead Sponsor
Actelion Pharmaceuticals Ltd.
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
All
Target Recruitment
128
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 < 450 m.

·Hemodynamic evaluation showing:
i.Mean pulmonary arterial pressure (mPAP) >= 25 mmHg
ii.Pulmonary capillary wedge pressure (PCWP) < 15 mmHg
iii.Pulmonary vascular resistance (PVR) at rest >= 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 =< 80 years of age (Women of childbearing potential must have a negative pre-treatment pregnancy test and use a reliable method of contraception).

·Anticoagulants at efficacious dose for at least 3 months prior to randomization.

·Signed informed consent prior to initiation of any study-mandated procedure.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

·Other forms of pulmonary hypertension including pulmonary hypertension related to sickle cell disease.

·Obstructive lung disease: FEV1/FVC < 0.5 after bronchodilation

·Severe restrictive lung disease: Total Lung Capacity < 60% of predicted value.

·Acute or chronic impairment (other than dyspnea), limiting the ability to comply with study requirements (in particular with 6MWT), e.g., angina pectoris, intermittent claudication.

·Symptomatic pulmonary embolism within 6 months prior to randomization.

·Pulmonary endarterectomy within 6 months prior to randomization.

·Psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements.

·Illness with a life expectancy of less than 6 months.

·Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C.

·AST and/or ALT > 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

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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