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

Pulmonary Hypertension Clinical Trial

— 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00319111
• Other study ID #: AC-052-370
• Secondary ID: BENEFIT OL
• Status: Completed
• Phase: Phase 3
• First received: April 26, 2006
• Last updated: November 29, 2012
• Start date: January 2006
• Est. completion date: April 2009

Study information

• Verified date: November 2012
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 151
• Est. completion date: April 2009
• Est. primary completion date: February 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary
• Pulmonary Hypertension

Intervention

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)

Locations

Country	Name	City	State
Australia	The Prince Charles Hospital	Brisbane
Australia	St. Vincent's Hospital	Darlinghurst	New South Wales
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Royal Perth Hospital	Perth	Western Australia
Austria	General Hospital of Vienna	Vienna
Belgium	University Hospital Erasme	Brussels
Belgium	University Hospital Gathuisberg	Leuven
Canada	University of Western Ontario	London	Ontario
Canada	The Ottawa Hospital	Ottawa	Ontario
Canada	Centre de Pneumologie de L'Hopital Laval	Sainte-Foy	Quebec
Canada	Toronto General Hospital	Toronto	Ontario
Canada	St. Paul's Hospital	Vancouver	British Columbia
Czech Republic	Charles University, Internal Medicine Department, (PAH unit)	Praha 2
France	Hopital Antoin Beclere	Clamart
France	Hôpital Louis Pradel	Lyon
Germany	University Hospital Giessen	Giessen
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Johannes Gutenberg University Hospital	Mainz
Italy	Policlinico S. Orsola-Malpighi	Bologna
Italy	San Matteo Hospital	Pavia
Italy	Ospedale di Cattinara	Trieste
Netherlands	Academic Medical Center	Amsterdam
Netherlands	St. Antonius Ziekennuis	Nieuwegein
Poland	Medical University of Warsaw	Warszawa
Spain	Hospital Clinico i Provincial	Barcelona
United Kingdom	Papworth Hospital	Cambridge
United Kingdom	Western Infirmary	Glasgow
United States	Duke University	Durham	North Carolina
United States	University of California at San Diego	La Jolla	California
United States	Mayo Clinic, Division of Cardiovascular Diseases and Internal Medicine	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes