Bosentan Effects in Inoperable Forms of Chronic Thromboembolic Pulmonary Hypertension

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00313222
• Date of registration: 10/04/2006
• Prospective Registration: No
• Primary sponsor: Actelion
• Public title: Bosentan Effects in Inoperable Forms of Chronic Thromboembolic Pulmonary Hypertension
• Scientific title: 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)
• Date of first enrolment: October 2005
• Target sample size: 157
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00313222
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment
• Phase: Phase 3

Countries of recruitment

Australia, Austria, Belgium, Canada, Czech Republic, France, Germany, Italy, Netherlands, Poland, Spain, United Kingdom, United States

Key inclusion & exclusion 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 < 450 m.

- Hemodynamic evaluation showing: Mean pulmonary arterial pressure (mPAP) >= 25 mmHg;
Pulmonary capillary wedge pressure (PCWP) < 15 mmHg; 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.

Exclusion Criteria:

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

- Obstructive lung disease: FEV1/FVC < 0.5 after bronchodilator.

- 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.



Age minimum: 18 Years
Age maximum: 80 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Chronic Thromboembolic Pulmonary Hypertension

Intervention(s)

Drug: bosentan

Primary Outcome(s)

Change from Baseline to Week 16 in 6-Minute Walk Test distance [Time Frame: Week 16]

Change from Baseline to Week 16 in Pulmonary Vascular Resistance at rest [Time Frame: Week 16]

Secondary Outcome(s)

Time to clinical worsening [Time Frame: Time to clinical worsening]

Change from Baseline to Week 16 in modified NYHA functional class [Time Frame: Week 16]

Secondary ID(s)

AC-052-366

Source(s) of Monetary Support

Please refer to primary and secondary sponsors