Clinical trial NCT00367770: BREATHE 5-OL: Tracleer (Bosentan) in Patients With Pulmonary Arterial Hypertension Related to Eisenmenger Physiology
Official title: A Multi-Center, Open-Label Extension Study to Protocol AC-052-405 to Evaluate the Safety and Efficacy of Tracleer (Bosentan) in Patients With Pulmonary Arterial Hypertension Related to Eisenmenger Physiology
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pulmonary Arterial Hypertension
Keywords: bosentan
PAH related to Eisenmenger physiology
Tracleer
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2006-08-23
Enrollment: 37
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This 6-month open label study will evaluate the long term safety of bosentan (via oxygen saturation) and efficacy (exercise capacity) in patients who have completed the BREATHE-5 study (PAH related to Eisenmenger physiology). Treatment duration is 6 months.

Detailed description: This is a multicenter, open-label, single -arm study with bosentan, initial dose of 62.5 mg b.i.d., with a target dose of 125 mg b.i.d. All patients will be assessed for eligibility during the baseline visit (same as Week 16, end of study BREATHE-5 visit), and will have the option to enter into the open-label extension study at a starting dose of 62.5 mg b.i.d., for safety reasons. Visit 2 is required as a safety visit to assess oxygen saturation (SpO2) after 1 week of bosentan treatment. Patients will return for Visit 4 after 4 weeks of treatment, and the dose will be up-titrated to 125 mg b.i.d. or maintained at 62.5 mg b.i.d. at the judgement of the investigator. Data will be collected for a total of 24 weeks or until the sponsor decides to stop the study. If the results from Study AC-052-403 or AC-052-405 demonstrate significant safety issues, this extension study may be terminated at the sponsor's request.

Eligibility criteria: Inclusion Criteria:

1. Patients stable with PAH upon completion of the BREATHE-5 randomized, double-blind, placebo- controlled 16-week study.
2. For female patients, only non-pregnant women who are surgically sterile, postmenopausal or have documented infertility (over 50 years of age and amenorrheic for at least 1 year), or those of childbearing potential using one of the following methods of contraception: Barrier-type devices (e.g., condom, diaphragm) used ONLY in combination with a spermicide. A double-barrier method is recommended; intrauterine devices (IUDs); oral or implanted contraceptives, if used in combination with a barrier method.
3. Patients providing written informed consent.

Exclusion Criteria:

1. Patients who withdrew prematurely from BREATHE-5, AC-052-405.
2. Patients who are pregnant or nursing.
3. Patients who are receiving epoprostenol or prostacyclin analogues, or are expected to receive any of these drugs during the study.
4. Patients with AST and/or ALT values greater than 3 times the upper limit of normal.
5. Patients with hemoglobin or hematocrit that is more than 30% below the normal range (patients with secondary polycythemia are permitted in the study).
6. Patients with systolic blood pressure \< 85 mm Hg.
7. Patients taking phosphodiesterase inhibitors, other endothelin receptor antagonists or are receiving another investigational product.
8. Patients active on organ transplant list.
9. Patients who are receiving or expected to receive glyburide, cyclosporin A or tacrolimus.
10. Patients not able to comply with the protocol or adhere to therapy.

Primary outcomes:
measure: Change in 6-minute Walk Distance
timeFrame: from baseline to week 24
measure: Change in Borg Dyspnea Index
timeFrame: from baseline to week 24
measure: Number of Participants With a Change in WHO Functional Class
timeFrame: from baseline to week 24
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: BACH Pulmonary Hypertension Service
state: Massachusetts
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital - Central Clinical School
city: Victoria
country: Australia
facility: The Royal Melbourne Hospital
city: Wien
country: Austria
facility: Universitatsklinikum fur Innere Medizin II
city: Leuven
country: Belgium
facility: UZ Gasthuisberg
city: Calgary
country: Canada
facility: The Peter Lougheed Centre
state: Alberta
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Paris
country: France
facility: Hospital Necker-Enfants Malades
city: Bad Oeynhausen
country: Germany
facility: Herzzentrum NRW
city: Munchen
country: Germany
facility: Deutsches Herzzentrum Munchen
city: Bologna
country: Italy
facility: University of Bologna
city: Pavia
country: Italy
facility: San Matteo Hospital
city: Groningen
country: Netherlands
facility: Academisch Ziekenhuis Groningen
city: Madrid
country: Spain
facility: Unidad Medico Quirurgica de Cardiologia - Edificio General
city: Glasgow
country: United Kingdom
facility: Scottish Vascular Unit - Western Infirmary
city: London
country: United Kingdom
facility: Royal Brompton Hospital
Study officials:
affiliation: BACH Pulmonary Hypertension Service, Boston, U.S.A.
name: Michael Landzberg, MD
role: STUDY_CHAIR
References: