Bosentan in Treatment of Pulmonary Arterial Hypertension

• Status: Completed
• Trial end date: 2008-02-01
• Target enrollment: 0
• Participant gender: All

Summary

Eisenmenger's syndrome presents as a severe clinical picture of polymorbidity that constitutes a great burden at the individual as well as the familial and social level. The combination of critically increased pulmonary vascular resistance, progressive pressure load of the right ventricle and disturbance of pulmonary gas exchange result in long-term polymorbidity. The objective of this study is to look into the effects of medium-term pulmonary pressure-lowering treatment with oral bosentan in patients with congenital heart defects and clinically relevant pulmonary arterial hypertension (PAH), taking advantage of extensive diagnostic procedures.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Competence Network for Congenital Heart Defects
• Collaborators: Actelion; German Federal Ministry of Education and Research
• Treatments: Bosentan

Criteria

Inclusion Criteria:

• Non-specific:

• Written informed consent obtained

• Specific:

• Age at least 18 years

• Presence of cyanosis with < 93 % arterial oxygen saturation (measured by transcutaneous pulse oximetry)

• Clinical indication for the invasive diagnostic procedures planned for the study is given; this is evaluated on the basis of observation before, during and after medicinal treatment)

• Presence of PAH as diagnosed by invasive methods with Rp:Rs > 0.75 measured at rest, before testing of pulmonary vasodilatory reserve

• One of the following diagnoses:

• non-corrected large congenital shunting defect at atrial, ventricular or arterial level: PAPVD, ASD, SVD, VSD, AVSD, TAC, APW, PDA, or a combination of these.

• Surgically corrected shunting defect (diagnoses as above) with significant residual defect

• Other diagnoses with univentricular physiology/haemodynamics.

Exclusion Criteria:

• Non-specific:

• pregnancy or lactation

• women of child-bearing age who are sexually active without practising reliable methods of contraception

• any disease or impairment that, in the opinion of the investigator, excludes a subject from participation

• substance abuse (alcohol, medicines, drugs)

• other medical, psychological or social circumstances that would adversely affect a patient's ability to participate adequately in the study or increase the risk to the patient or others in the case of participation.

• insufficient compliance

• subjects in whom MRI cannot be performed (contrast medium allergy, claustrophobia, cardiac pacemaker)

• subjects who are not able to perform CPX

• Specific:

• pulmonary hypertension of any aetiology other than those specified in the inclusion criteria

• subjects with known intolerance of NO or iloprost or their constituents

• acute decompensated heart failure within 7 days before the invasive procedure

• haemodynamic instability that would increase the risk of pulmonary arterial reactivity testing

• arterial hypotension

• anaemia (Hb < 10 g/dl)

• decompensated symptomatic polycythaemia

• thrombocytopenia (< 50,000/μl)

• secondary impairment of organic (renal, hepatic) function

• other sources of pulmonary blood flow which render the measurement of the blood flow to the lungs and pulmonary vascular resistance impossible

• obstruction of pulmonary blood outflow

• left ventricular diseases

• significant valvular diseases other than tricuspid or pulmonary regurgitation

• pericardial constriction

• history of stroke, myocardial infarction or life-threatening arrhythmia within 6 months before screening

• bronchopulmonary dysplasia or other chronic lung diseases

• history of significant pulmonary embolism

• other relevant diseases (e.g. HIV infection)

• trisomy 21

• Prohibited concomitant medication: Any medication listed below which has not been discontinued at least 30 days prior to screening.

• Unspecified or other significant medication (e.g. medication for diabetes or immunosuppression)

• Unstable medication, recent changes in dosage regimen

• Drugs to treat pulmonary hypertension (endothelin receptor antagonists, PDE-5 antagonists, prostanoids. (Specific pulmonary vasodilators during cardiac catheterisation are allowed.)

• Other medication with vascular action

• Medication that is not compatible with bosentan or that interferes with its metabolism (inhibitors of CYP2C9 or CYP3A4) or that, in the investigator's opinion, may interfere with bosentan treatment