Pulmonary arterial hypertension Exercise induced Congenital heart disease Advanced treatment Cardiopulmonary exercise test Pulmonale arteriële hypertensie Inspanningsgebonden Congenitale hartziekten Cardiopulmonale inspanningstest
Conditions
Interventions
When all baseline procedures have been performed and the investigator has observed that all inclusion and none of the exclusion criteria apply, patients are randomised by the investigator using a comp
2. 6 months of treatment with placebo twice a day.
The starting dosage of bosentan is 62,5 mg twice a day. Trial medication is doubled after 4 weeks to reach study dose, after checking liver paramete
Sponsors
Academic Medical Center - University of Amsterdam
Eligibility
Inclusion criteria
Inclusion criteria: In order to be eligible to participate in this study, a subject must meet all of the following criteria: 1. Adult (>18 years) and mentally competent; 2. Open or closed septal defect (ASD I/II, VSD, AVSD); 3. Open or closed systemic-to-pulmonary shunt (PDA); 4. Presence of X-PAH: A. One of the following criteria, at peak exercise: i. mPAP > 34 mmHg with CO ≤ 10 l/min; ii. mPAP > 40 mmHg with CO ≤ 15 l/min; iii. mPAP > 45 mmHg with CO ≤ 20 l/min; iiii. mPAP > 50 mmHg with CO ≤ 30 l/min. B. And a PVR (slope pressure/flow plot) of > 2.5 mmHg/l/min.
Exclusion criteria
Exclusion criteria: A potential subject who meets any of the following criteria will be excluded from participation in this study: 1. Incapable of giving informed consent; 2. Pregnancy or lactation (a pregnancy test is offered to every female patient within fertile age); 3. Women of child-bearing age who are sexually active without practising reliable methods of contraception; 4. Substance abuse (alcohol, medicines, drugs); 5. Subjects who are not able to perform cardiopulmonary exercise testing; 6. Any cardiac operation < 6 months before inclusion; 7. PAH of any aetiology other than the one specified in the inclusion criteria; 8. Impairment of organic function (renal, hepatic); 9. Arterial hypotension (systolic blood pressure < 85mmHg); 10. Anaemia (Hb < 10g/L, or <6.21 mmol/L); 11. Significant valvular disease, other than tricuspid or pulmonary regurgitation; 12. Chronic lung disease or total lung capacity < 80% predicted value; 13. History of significant pulmonary embolism; 14. Other relevant diseases (HIV infection, Hep B/C infection); 15. Subjects with known intolerance to bosentan or their constituents; 16. Prohibited medication: Any medication listed below which has not been discontinued at least 30 days prior to inclusion: A. Unspecified or other significant medication (glyburide or immunosuppression); B. PAH therapy (endothelin receptor antagonists, PDE-5 inhibitors, prostanoids); C. Medication which is not compatible with bosentan or interferes with its metabolism (inhibitors of CYP2C9, CYP3A4) or medication which may interfere with bosentan treatment according to the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary objective of this study is to determine change in mean pulmonary arterial pressure at peak exercise in adult congenital heart disease patients with exercise-induced pulmonary arterial hypertension before and after treatment with bosentan, compared to patients treated with placebo. | — |
Secondary
| Measure | Time frame |
|---|---|
| To determine: 1. Cardiopulmonary exercise capacity: i.e. peak oxygen consumption, VE/VCO2 ratio, O2 pulse; 2. Pulmonary hemodynamics: i.e. systolic pulmonary arterial pressure, pulmonary vascular resistance, pressure-flow relationships during and at peak exercise; 3. Right ventricular function: i.e. TAPSE, TEI index, TDI-S, right ventricular dimensions; 4. Laboratory parameters: i.e. NT-pro BNP, troponin T; 5. NYHA functional class; 6. Quality of life: assessed by TAAQOL-CHD, SF-36 and Minnesota CHD-HF questionnaire. | — |
Contacts
Public ContactA.C.M.J. Riel, van
Outcome results
None listed