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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Actelion
ClinicalTrials.gov Identifier:
NCT00319111
First received: April 26, 2006
Last updated: November 29, 2012
Last verified: November 2012
  Purpose

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


Condition Intervention Phase
Pulmonary Hypertension
Drug: bosentan
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Long-term Open-label Extension Study in Patients With Inoperable Chronic Thromboembolic Pulmonary Hypertension (CTEPH) Who Completed Protocol AC-052-366 (BENEFIT, NCT00313222)

Resource links provided by NLM:


Further study details as provided by Actelion:

Primary Outcome Measures:
  • Change From Baseline to All Assessed Time Points in 6-minute Walk Test (6MWT) Distance [ Time Frame: Until discontinuation of study drug, up to 3.3 years ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline to All Assessed Time Points in Borg Dyspnea Index [ Time Frame: Until discontinuation of study drug, up to 3.3 years ] [ Designated as safety issue: No ]
    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]).

  • Disease Severity - Number of Patients Showing Improvement by One Class or More in World Health Organisation (WHO) Functional Classification of Pulmonary Hypertension (PH) [ Time Frame: Until discontinuation of study drug, up to 3.3 years ] [ Designated as safety issue: No ]

    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.


  • Time to Clinical Worsening up to End-of-study [ Time Frame: Until discontinuation of study drug, up to 3.3 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Number of Patients With an Adverse Event(s) Leading to Premature Discontinuation of Study Medication [ Time Frame: Until discontinuation of study drug, up to 3.3 years ] [ Designated as safety issue: Yes ]
  • Number of Patients Experiencing a Serious Adverse Event(s) up to 28 Days After Study Medication Discontinuation [ Time Frame: 28 days after discontinuation of study drug, up to 3.3 years ] [ Designated as safety issue: Yes ]
  • Occurrence of Liver Function Test and Hemoglobin Abnormality [ Time Frame: Until discontinuation of study drug, up to 3.3 years ] [ Designated as safety issue: Yes ]
    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


Enrollment: 151
Study Start Date: January 2006
Study Completion Date: April 2009
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00319111

  Show 30 Study Locations
Sponsors and Collaborators
Actelion
  More Information

No publications provided

Responsible Party: Actelion
ClinicalTrials.gov Identifier: NCT00319111     History of Changes
Other Study ID Numbers: AC-052-370, BENEFIT OL
Study First Received: April 26, 2006
Results First Received: May 24, 2012
Last Updated: November 29, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Actelion:
pulmonary hypertension
bosentan
BENEFIT
CTEPH
inoperable chronic thromboembolic pulmonary hypertension (CTEPH)

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Bosentan
Antihypertensive Agents
Cardiovascular Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014