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BREATHE 5-OL: Tracleer (Bosentan) in Patients With Pulmonary Arterial Hypertension Related to Eisenmenger Physiology

Phase 4
Completed
Conditions
Pulmonary Arterial Hypertension
Interventions
Registration Number
NCT00367770
Lead Sponsor
Actelion
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
37
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
TracleerTracleer®The starting dose for all patients will be 62.5 mg b.i.d. At the Week 4 visit, patients who were started on 62.5 mg b.i.d. will be uptitrated to 125 mg b.i.d. if the 62.5 mg b.i.d. dose was well-tolerated.
Primary Outcome Measures
NameTimeMethod
Change in 6-minute Walk Distancefrom baseline to week 24
Change in Borg Dyspnea Indexfrom baseline to week 24

Borg scale a numerical scale for assessing dyspnea, from 0 representing no dyspnea to 10 as maximal dyspnea.

Number of Participants With a Change in WHO Functional Classfrom baseline to week 24

Number of participants with a change in WHO functional class from baseline to week 24.

A change from a higher to a lower functional class (i.e. III to II, III to I or II to I) is considered as an improvement.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (17)

Academisch Ziekenhuis Groningen

🇳🇱

Groningen, Netherlands

Hospital Necker-Enfants Malades

🇫🇷

Paris, France

Texas Children's Hospital

🇺🇸

Houston, Texas, United States

BACH Pulmonary Hypertension Service

🇺🇸

Boston, Massachusetts, United States

Royal Prince Alfred Hospital - Central Clinical School

🇦🇺

Camperdown, Australia

The Peter Lougheed Centre

🇨🇦

Calgary, Alberta, Canada

Toronto General Hospital

🇨🇦

Toronto, Ontario, Canada

Deutsches Herzzentrum Munchen

🇩🇪

Munchen, Germany

Herzzentrum NRW

🇩🇪

Bad Oeynhausen, Germany

University of Bologna

🇮🇹

Bologna, Italy

San Matteo Hospital

🇮🇹

Pavia, Italy

Unidad Medico Quirurgica de Cardiologia - Edificio General

🇪🇸

Madrid, Spain

Scottish Vascular Unit - Western Infirmary

🇬🇧

Glasgow, United Kingdom

Universitatsklinikum fur Innere Medizin II

🇦🇹

Wien, Austria

UZ Gasthuisberg

🇧🇪

Leuven, Belgium

The Royal Melbourne Hospital

🇦🇺

Victoria, Australia

Royal Brompton Hospital

🇬🇧

London, United Kingdom

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