Pulmonary Arterial Hypertension Related to Eisenmenger Physiology
Conditions
Keywords
pulmonary arterial hypertension, Eisenmenger physiology, bosentan
Brief summary
This study evaluates the effects of bosentan on oxygen saturation, hemodynamics and exercise capacity in patients with pulmonary arterial hypertension related to Eisenmenger physiology. Patients receive bosentan or placebo for 16 weeks.
Interventions
DRUGbosentan
Sponsors
Actelion
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female patients at least 12 years with a body weight at least 40 kg (inclusive) and with a functional class III (1998 WHO classification). 2. Patients with pulmonary arterial hypertension related to Eisenmenger physiology echocardiographically established as atrial septal defect at least 2 cm effective diameter and/or ventricular septal defect at least 1 cm effective diameter; PAH confirmed via cardiac catheterization: mean pulmonary arterial pressure \>25 mm Hg, pulmonary capillary wedge pressure \<15 mm Hg and pulmonary vascular resistance \>3 mm Hg/l/min. 3. Patients with documented oxygen saturation up to 90%, and \>70% (at rest, with room air). 4. Patients able to perform a 6-minute walk test at least 150 m, and up to 450 m. 5. Patients stable for at least 3 months prior to screening. 6. Bosentan naïve patients. 7. Female patients who are surgically sterile, postmenopausal or have documented infertility. 8. Female patients 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. 9. Patients providing written informed consent.
Exclusion criteria
1. Pregnant patients, nursing mothers. 2. Patients with left ventricular dysfunction (ejection fraction \<40%). 3. Patients with restrictive lung disease (TLC\<70% predicted); obstructive lung disease (FEV1\<70% predicted, with FEV1/FVC\<60%) 4. Patients with systolic blood pressure \< 85 mm Hg. 5. Patients with other conditions that may affect the ability to perform a 6-minute walk test. 6. Patients unable to provide informed consent and comply with the patient protocol. 7. Patients with known coronary arterial disease. 8. Patients with serum creatinine \>125 µM/l. 9. Patients with iron deficiency (serum ferritin \<10 ng/ml) unless corrected by iron supplement. 10. Patients with hemoglobin or hematocrit that is more than 30% below the normal range (patients with secondary polycythemia are permitted). 11. Patients with AST and/or ALT values greater than 3 times the upper limit of normal. 12. Patients who have started or stopped treatment for PAH within one month of screening, excluding anticoagulation. 13. Patients who are receiving glyburide (glibenclamide), cyclosporine A or tacrolimus at inclusion or are expected to receive any of these drugs during the study. 14. Patients who are receiving vasodilators including, but not limited to epoprostenol or prostacyclin analogues, or are expected to receive any of these drugs during the study. 15. Patients active on organ transplant lists. 16. Patients taking phosphodiesterase inhibitors or endothelin receptor antagonists (other than bosentan) or any other investigational drugs/devices. 17. Patients with planned surgical intervention during the study period. 18. Cardiac catheterization-specific
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline to Week 16 in oxygen saturation at rest with room air | — |
| Change from baseline to Week 16 in indexed pulmonary vascular resistance | — |
Secondary
| Measure | Time frame |
|---|---|
| Changes from baseline to Week 16 in cardiac hemodynamics | — |
Outcome results
None listed