Bosentan in Exercise Induced Pulmonary Arterial Hypertension in Congenital Heart Disease

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 40

Inclusion Criteria

In order to be eligible to participate in this study, a subject must meet all of the following criteria:
- adult (>18 years) and mentally competent
- Open or closed septal defect (ASD I/II, VSD, AVSD)
- Open or closed systemic-to-pulmonary shunt (PDA)
- Negative pregnancy test
- Presence of X-PAH, including one of the following criteria, at peak exercise.
* mPAP > 34 mmHg with CO <= 10 l/min
* mPAP > 40 mmHg with CO <= 15 l/min
* mPAP > 45 mmHg with CO <= 20 l/min
* mPAP > 50 mmHg with CO <= 30 l/min
* PVR (slope pressure/flow plot) of > 2.5 mmHg/l/min during exercise

Exclusion Criteria

A potential subject who meets any of the following criteria will be excluded from participation in this study:
- Incapable of giving informed consent
- Pregnancy or lactation (a pregnancy test is offered to every female patient within fertile age)
- Women of child-bearing age who are sexually active without practising reliable methods of contraception. The use of oral contraceptives only, is not considered reliable.
- Substance abuse (alcohol, medicines, drugs)
- Subjects who are not able to perform cardiopulmonary exercise testing
- Any cardiac operation <6 months before inclusion
- PAH of any aetiology other than the one specified in the inclusion criteria
- Left ventricular ejection fraction < 30%
- Significant impairment of renal function (GFR < 30 ml/min/1.73m2)
- Moderate to severe liver disease: Child Pugh class B or C
- Raised plasma transaminases level > three times upper normal limit
- Arterial hypotension (systolic blood pressure < 85mmHg)
- Anaemia (Hb < 10g/L, or <6.21 mmol/L)
- Significant valvular disease, other than tricuspid or pulmonary regurgitation
- Chronic lung disease or total lung capacity < 80% predicted value
- History of significant pulmonary embolism
- Other relevant diseases (HIV infection, Hep B/C infection)
- Subjects with known intolerance to bosentan or their constituents
- Prohibited medication: any medication listed below which has not been discontinued at least 30 days prior to inclusion
o Unspecified or other significant medication (glybenclamide or immunosuppression)
o PAH therapy (endothelin receptor antagonists, PDE-5 inhibitors, prostanoids)
o Medication which is not compatible with bosentan or interferes with its metabolism (inhibitors or inducers of CYP2C9, CYP3A4) or medication which may interfere with bosentan treatment according to the investigator

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>To determine:<br /><br>• change in mean pulmonary arterial pressure (mPAP) at peak exercise<br /><br>o measured by means of transthoracic echocardiography at 3 and 6 months<br /><br>followup: mPAP = 0.6 x systolic PAP.<br /><br>o peak exercise is defined as 80% of maximum calculated heart rate: peak<br /><br>exercise=0.8*(220-age)</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>To determine:<br /><br>• Cardiopulmonary exercise capacity (i.e. peak oxygen consumption, VE/VCO2<br /><br>ratio, O2 pulse)<br /><br>• Pulmonary hemodynamics (i.e. systolic pulmonary arterial pressure, pulmonary<br /><br>vascular resistance, pressure-flow relationships during and at peak exercise)<br /><br>• Right ventricular function (i.e. TAPSE, TEI index, TDI-S, right ventricular<br /><br>dimensions)<br /><br>• Laboratory parameters (i.e. NT-pro BNP, troponin T)<br /><br>• NYHA functional class<br /><br>• Quality of life (assessed by TAAQOL-CHD, SF-36 and Minnesota CHD-HF<br /><br>questionnaire)<br /><br>• Demographics (age, gender, marital status, work, income); assessed by<br /><br>demographic questionnaire.</p><br>