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

Phase 3
Completed
Conditions
Pulmonary Hypertension
Interventions
Registration Number
NCT00319111
Lead Sponsor
Actelion
Brief Summary

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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
151
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

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
BosentanbosentanOpen label bosentan treatment
Primary Outcome Measures
NameTimeMethod
Change From Baseline to All Assessed Time Points in 6-minute Walk Test (6MWT) DistanceUntil discontinuation of study drug, up to 3.3 years

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 IndexUntil discontinuation of study drug, up to 3.3 years

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)Until discontinuation of study drug, up to 3.3 years

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-studyUntil discontinuation of study drug, up to 3.3 years

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
NameTimeMethod
Number of Patients With an Adverse Event(s) Leading to Premature Discontinuation of Study MedicationUntil 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 Discontinuation28 days after discontinuation of study drug, up to 3.3 years
Occurrence of Liver Function Test and Hemoglobin AbnormalityUntil discontinuation of study drug, up to 3.3 years

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

Trial Locations

Locations (30)

Royal Perth Hospital

🇦🇺

Perth, Western Australia, Australia

Hôpital Louis Pradel

🇫🇷

Lyon, France

General Hospital of Vienna

🇦🇹

Vienna, Austria

University of Western Ontario

🇨🇦

London, Ontario, Canada

University Hospital Giessen

🇩🇪

Giessen, Germany

Centre de Pneumologie de L'Hopital Laval

🇨🇦

Sainte-Foy, Quebec, Canada

Ospedale di Cattinara

🇮🇹

Trieste, Italy

Hopital Antoin Beclere

🇫🇷

Clamart, France

St. Antonius Ziekennuis

🇳🇱

Nieuwegein, Netherlands

Duke University

🇺🇸

Durham, North Carolina, United States

University Hospital Gathuisberg

🇧🇪

Leuven, Belgium

Medizinische Hochschule Hannover

🇩🇪

Hannover, Germany

Mayo Clinic, Division of Cardiovascular Diseases and Internal Medicine

🇺🇸

Rochester, Minnesota, United States

University of California at San Diego

🇺🇸

La Jolla, California, United States

St. Vincent's Hospital

🇦🇺

Darlinghurst, New South Wales, Australia

The Alfred Hospital

🇦🇺

Melbourne, Victoria, Australia

The Prince Charles Hospital

🇦🇺

Brisbane, Australia

University Hospital Erasme

🇧🇪

Brussels, Belgium

St. Paul's Hospital

🇨🇦

Vancouver, British Columbia, Canada

The Ottawa Hospital

🇨🇦

Ottawa, Ontario, Canada

Toronto General Hospital

🇨🇦

Toronto, Ontario, Canada

Charles University, Internal Medicine Department, (PAH unit)

🇨🇿

Praha 2, Czech Republic

Policlinico S. Orsola-Malpighi

🇮🇹

Bologna, Italy

San Matteo Hospital

🇮🇹

Pavia, Italy

Johannes Gutenberg University Hospital

🇩🇪

Mainz, Germany

Academic Medical Center

🇳🇱

Amsterdam, Netherlands

Hospital Clinico i Provincial

🇪🇸

Barcelona, Spain

Medical University of Warsaw

🇵🇱

Warszawa, Poland

Papworth Hospital

🇬🇧

Cambridge, United Kingdom

Western Infirmary

🇬🇧

Glasgow, United Kingdom

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