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

Primary Purpose

Pulmonary Hypertension

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
bosentan
Sponsored by
Actelion
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Hypertension focused on measuring pulmonary hypertension, bosentan, BENEFIT, CTEPH, inoperable chronic thromboembolic pulmonary hypertension (CTEPH)

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of California at San Diego
  • Mayo Clinic, Division of Cardiovascular Diseases and Internal Medicine
  • Duke University
  • St. Vincent's Hospital
  • The Alfred Hospital
  • Royal Perth Hospital
  • The Prince Charles Hospital
  • General Hospital of Vienna
  • University Hospital Erasme
  • University Hospital Gathuisberg
  • St. Paul's Hospital
  • University of Western Ontario
  • The Ottawa Hospital
  • Toronto General Hospital
  • Centre de Pneumologie de L'Hopital Laval
  • Charles University, Internal Medicine Department, (PAH unit)
  • Hopital Antoin Beclere
  • Hôpital Louis Pradel
  • University Hospital Giessen
  • Medizinische Hochschule Hannover
  • Johannes Gutenberg University Hospital
  • Policlinico S. Orsola-Malpighi
  • San Matteo Hospital
  • Ospedale di Cattinara
  • Academic Medical Center
  • St. Antonius Ziekennuis
  • Medical University of Warsaw
  • Hospital Clinico i Provincial
  • Papworth Hospital
  • Western Infirmary

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Bosentan

Arm Description

Open label bosentan treatment

Outcomes

Primary Outcome Measures

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.
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]).
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.
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.

Secondary Outcome Measures

Number of Patients With an Adverse Event(s) Leading to Premature Discontinuation of Study Medication
Number of Patients Experiencing a Serious Adverse Event(s) up to 28 Days After Study Medication Discontinuation
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

Full Information

First Posted
April 26, 2006
Last Updated
November 29, 2012
Sponsor
Actelion
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1. Study Identification

Unique Protocol Identification Number
NCT00319111
Brief Title
Bosentan in Patients With Inoperable Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
Acronym
BENEFIT OL
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)
Study Type
Interventional

2. Study Status

Record Verification Date
November 2012
Overall Recruitment Status
Completed
Study Start Date
January 2006 (undefined)
Primary Completion Date
February 2009 (Actual)
Study Completion Date
April 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Actelion

4. Oversight

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Hypertension
Keywords
pulmonary hypertension, bosentan, BENEFIT, CTEPH, inoperable chronic thromboembolic pulmonary hypertension (CTEPH)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
151 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Bosentan
Arm Type
Experimental
Arm Description
Open label bosentan treatment
Intervention Type
Drug
Intervention Name(s)
bosentan
Intervention Description
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)
Primary Outcome Measure Information:
Title
Change From Baseline to All Assessed Time Points in 6-minute Walk Test (6MWT) Distance
Description
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.
Time Frame
Until discontinuation of study drug, up to 3.3 years
Title
Change From Baseline to All Assessed Time Points in Borg Dyspnea Index
Description
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]).
Time Frame
Until discontinuation of study drug, up to 3.3 years
Title
Disease Severity - Number of Patients Showing Improvement by One Class or More in World Health Organisation (WHO) Functional Classification of Pulmonary Hypertension (PH)
Description
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 Frame
Until discontinuation of study drug, up to 3.3 years
Title
Time to Clinical Worsening up to End-of-study
Description
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.
Time Frame
Until discontinuation of study drug, up to 3.3 years
Secondary Outcome Measure Information:
Title
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
Title
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
Title
Occurrence of Liver Function Test and Hemoglobin Abnormality
Description
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
Time Frame
Until discontinuation of study drug, up to 3.3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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
Facility Information:
Facility Name
University of California at San Diego
City
La Jolla
State/Province
California
ZIP/Postal Code
92037-1300
Country
United States
Facility Name
Mayo Clinic, Division of Cardiovascular Diseases and Internal Medicine
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
St. Vincent's Hospital
City
Darlinghurst
State/Province
New South Wales
ZIP/Postal Code
2010
Country
Australia
Facility Name
The Alfred Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Facility Name
Royal Perth Hospital
City
Perth
State/Province
Western Australia
ZIP/Postal Code
6000
Country
Australia
Facility Name
The Prince Charles Hospital
City
Brisbane
ZIP/Postal Code
4032
Country
Australia
Facility Name
General Hospital of Vienna
City
Vienna
ZIP/Postal Code
1180
Country
Austria
Facility Name
University Hospital Erasme
City
Brussels
ZIP/Postal Code
1070
Country
Belgium
Facility Name
University Hospital Gathuisberg
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
St. Paul's Hospital
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6Z 1Y6
Country
Canada
Facility Name
University of Western Ontario
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 4G5
Country
Canada
Facility Name
The Ottawa Hospital
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1Y 4W7
Country
Canada
Facility Name
Toronto General Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2N2
Country
Canada
Facility Name
Centre de Pneumologie de L'Hopital Laval
City
Sainte-Foy
State/Province
Quebec
ZIP/Postal Code
G1V 4G5
Country
Canada
Facility Name
Charles University, Internal Medicine Department, (PAH unit)
City
Praha 2
ZIP/Postal Code
128 08
Country
Czech Republic
Facility Name
Hopital Antoin Beclere
City
Clamart
ZIP/Postal Code
92140
Country
France
Facility Name
Hôpital Louis Pradel
City
Lyon
ZIP/Postal Code
69000
Country
France
Facility Name
University Hospital Giessen
City
Giessen
ZIP/Postal Code
35392
Country
Germany
Facility Name
Medizinische Hochschule Hannover
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Johannes Gutenberg University Hospital
City
Mainz
ZIP/Postal Code
55101
Country
Germany
Facility Name
Policlinico S. Orsola-Malpighi
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Facility Name
San Matteo Hospital
City
Pavia
ZIP/Postal Code
27100
Country
Italy
Facility Name
Ospedale di Cattinara
City
Trieste
ZIP/Postal Code
34149
Country
Italy
Facility Name
Academic Medical Center
City
Amsterdam
ZIP/Postal Code
1100 DE
Country
Netherlands
Facility Name
St. Antonius Ziekennuis
City
Nieuwegein
ZIP/Postal Code
3430 EM
Country
Netherlands
Facility Name
Medical University of Warsaw
City
Warszawa
ZIP/Postal Code
01-138
Country
Poland
Facility Name
Hospital Clinico i Provincial
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Papworth Hospital
City
Cambridge
ZIP/Postal Code
CB3 8RE
Country
United Kingdom
Facility Name
Western Infirmary
City
Glasgow
ZIP/Postal Code
G11 5AA
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

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

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