Bosentan in Patients With Inoperable Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

Study Overview
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Brief Summary
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The present trial investigates the long-term safety, tolerability and efficacy of bosentan in patients with inoperable CTEPH.

Official Title
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Long-term Open-label Extension Study in Patients With Inoperable Chronic Thromboembolic Pulmonary Hypertension (CTEPH) Who Completed Protocol AC-052-366 (BENEFIT, NCT00313222)

Conditions
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Pulmonary Hypertension

Intervention / Treatment
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* Drug: bosentan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients having completed the 16-week treatment period of protocol AC-052-366 (NCT00313222) Signed informed consent Exclusion Criteria: Any major violation of protocol AC-052-366 (NCT00313222) Pregnancy or breast-feeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bosentan<br>Open label bosentan treatment | Drug: bosentan<br>* Oral bosentan Initial dose: 62.5 mg twice a day (b.i.d.) for 4 weeks for all patients Maintenance dose: 125 mg b.i.d. (62.5 mg b.i.d. if weight < 40 kg)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to All Assessed Time Points in 6-minute Walk Test (6MWT) Distance | Exercise capacity was assessed using the 6MWT. Area used for testing had to be a minimum of 30m in length and 2-3m in width, with 3m gradations. Areas were well ventilated with air temperature controlled. The test was administered at the same time of day and by the same tester throughout the study. The tester measured the distance walked by non-encouraged patients during the timed 6min period. If the test was stopped before 6 minutes, the main reason for stopping the test was recorded. The tester measured the distance walked by patients during the timed 6min period. | Until discontinuation of study drug, up to 3.3 years | 
| Change From Baseline to All Assessed Time Points in Borg Dyspnea Index | Maximal dyspnea during the walk test was assessed by the patient using the Borg dyspnea index. Immediately following each walk test, patients rated perceived maximal breathlessness during the walk test on a 12-point scale (0 [nothing at all], 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 [maximum ever experienced]). | Until discontinuation of study drug, up to 3.3 years | 
| Disease Severity - Number of Patients Showing Improvement by One Class or More in World Health Organisation (WHO) Functional Classification of Pulmonary Hypertension (PH) | Disease severity was assessed by WHO classification of PH criteria: Class I: no limitation of physical activity (PA). Ordinary PA: no undue dyspnea/fatigue, chest pain, near syncope. Class II: slight limitation of PA. Comfortable at rest. Ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class III: marked limitation of PA. Comfortable at rest. Less than ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class IV: inability to carry out PA without symptoms. Right heart failure. Dyspnea/fatigue may even have been present at rest. Discomfort increased by any PA. | Until discontinuation of study drug, up to 3.3 years | 
| Time to Clinical Worsening up to End-of-study | An event of clinical worsening was defined as death during the treatment period, a treatment-emergent adverse event that led to permanent discontinuation of study treatment and with outcome death, hospitalization due to worsening pulmonary hypertension, or lung transplantation. Patients are censored at 1 day after the end of treatment or at day of pulmonary endarterectomy if earlier. | Until discontinuation of study drug, up to 3.3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With an Adverse Event(s) Leading to Premature Discontinuation of Study Medication |  | Until discontinuation of study drug, up to 3.3 years | 
| Number of Patients Experiencing a Serious Adverse Event(s) up to 28 Days After Study Medication Discontinuation |  | 28 days after discontinuation of study drug, up to 3.3 years | 
| Occurrence of Liver Function Test and Hemoglobin Abnormality | Number of patients with an increase in liver aminotransferases to >3 times upper limit of normal (ULN) or a decrease in hemoglobin concentration to ≤10 g/dL | Until discontinuation of study drug, up to 3.3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pulmonary hypertension, bosentan, BENEFIT, CTEPH, inoperable chronic thromboembolic pulmonary hypertension (CTEPH)