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

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

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

Study Overview

• Status: Completed
• Conditions: Pulmonary Hypertension
• Intervention / Treatment: Drug: bosentan

• Study Type: Interventional
• Enrollment (Actual): 151
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Brisbane, Australia, 4032
    • The Prince Charles Hospital
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • St. Vincent's Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
  • Western Australia
    • Perth, Western Australia, Australia, 6000
      • Royal Perth Hospital
• Austria
  • Vienna, Austria, 1180
    • General Hospital of Vienna
• Belgium
  • Brussels, Belgium, 1070
    • University Hospital Erasme
  • Leuven, Belgium, 3000
    • University Hospital Gathuisberg
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • St. Paul's Hospital
  • Ontario
    • London, Ontario, Canada, N6A 4G5
      • University of Western Ontario
    • Ottawa, Ontario, Canada, K1Y 4W7
      • The Ottawa Hospital
    • Toronto, Ontario, Canada, M5G 2N2
      • Toronto General Hospital
  • Quebec
    • Sainte-Foy, Quebec, Canada, G1V 4G5
      • Centre de Pneumologie de L'Hopital Laval
• Czech Republic
  • Praha 2, Czech Republic, 128 08
    • Charles University, Internal Medicine Department, (PAH unit)
• France
  • Clamart, France, 92140
    • Hopital Antoin Beclere
  • Lyon, France, 69000
    • Hôpital Louis Pradel
• Germany
  • Giessen, Germany, 35392
    • University Hospital Giessen
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Mainz, Germany, 55101
    • Johannes Gutenberg University Hospital
• Italy
  • Bologna, Italy, 40138
    • Policlinico S. Orsola-Malpighi
  • Pavia, Italy, 27100
    • San Matteo Hospital
  • Trieste, Italy, 34149
    • Ospedale di Cattinara
• Netherlands
  • Amsterdam, Netherlands, 1100 DE
    • Academic Medical Center
  • Nieuwegein, Netherlands, 3430 EM
    • St. Antonius Ziekennuis
• Poland
  • Warszawa, Poland, 01-138
    • Medical University of Warsaw
• Spain
  • Barcelona, Spain, 08035
    • Hospital Clinico i Provincial
• United Kingdom
  • Cambridge, United Kingdom, CB3 8RE
    • Papworth Hospital
  • Glasgow, United Kingdom, G11 5AA
    • Western Infirmary
• United States
  • California
    • La Jolla, California, United States, 92037-1300
      • University of California at San Diego
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic, Division of Cardiovascular Diseases and Internal Medicine
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bosentan; Open label bosentan treatment	Drug: bosentan; 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)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Actelion

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (Actual): February 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: April 26, 2006
• First Submitted That Met QC Criteria: April 26, 2006
• First Posted (Estimated): April 27, 2006

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 31, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: pulmonary hypertension; bosentan; CTEPH; BENEFIT; inoperable chronic thromboembolic pulmonary hypertension (CTEPH)
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Endothelin Receptor Antagonists; Bosentan
• Other Study ID Numbers: AC-052-370; BENEFIT OL