Repaired (after the age of 40) atrial septal defect patients older than 40 years with evidence of mild pulmonary vascular disese as assessed by bicycle stress echocardiography. MedDRA version: 12.1 Level: LLT Classification code 10003664 Term: Atrial septal defect MedDRA version: 12.1 Level: LLT Classification code 10037400 Term: Pulmonary hypertension
Conditions
Interventions
Trade Name: Tracleer
Product Name: bosentan
Pharmaceutical Form: Coated tablet
CAS Number: 157212-55-0
Other descriptive name: BOSENTAN MONOHYDRATE
Concentration unit: mg milligram(s)
Concentration ty
Sponsors
University Hospitals Leuven
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Signed informed consent by patient prior to initiation of any study-mandated procedure. • Male or female patients older than 40 years of age AND older than 40 years at the time of repair • Women of childbearing potential must have a negative pre-treatment pregnancy test and must use a reliable method of contraception during study treatment and for at least 3 months after study treatment termination. Reliable methods of contraception are Barrier type devices (female condom, diaphragm, contraceptive sponge) only in combination with a spermicide. Intra-uterine devices Hormone-based contraceptives. Abstinention, rhythm method, and contraception by the partner alone are not considered as reliable methods for contraception Women not of childbearing potential are defined as postmenopausal (amenorrhea for at least 1 year), or documented surgically or naturally sterile. • Presence of mild pulmonary vascular disease Slope of right ventricular systolic pressure and cardiac output greater than 4.5 mmHg/L/min Right ventricular systolic pressure greater than 40 mmHg at rest Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Non-specific o Pregnancy or lactation o Women of child-bearing age who are sexually active without practising reliable methods of contraception o Any disease or impairment that, in the opinion of the investigator, excludes a subject from participation o Substance abuse (alcohol, medicines, drugs) o 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 o Insufficient compliance o Subjects who are not able to perform cardiopulmonary exercise testing • Specific o ASD repair < 6 months before inclusion o PAH of any aetiology other than the one specified in the inclusion criteria o Impairment of organic function (renal, hepatic) o Arterial hypotension (systolic blood pressure < 85 mmHg) o Anaemia (Hb< 10 g/dl) o Decompensated symptomatic polycythemia o Thrombocytopenia (< 50000/µl) o Significant valvular diseases, other than tricuspid or pulmonary regurgitation o Chronic lung disease or total lung capacity < 80% of predicted value o History of significant pulmonary embolism o Other relevant diseases (HIV infection, Hep B/C infection) o Subjects with known intolerance to bosentan or their constituents o Prohibited medication: any medication listed below which has not been discontinued at least 30 days prior to screening ? Unspecified or other significant medication (glyburide or immunosuppression) ? Drugs to treat PAH (endothelin receptor antagonists, PDE-5 antagonists, prostanoids) ? Medication that is not compatible with bosentan or that interferes with its metabolism (inhibitors of CYP2C9 or CYP3A4) or that, in the investigator’s opninion, may interfere with bosentan treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To prospectively assess the efficacy of the dual endothelin receptor antagonist bosentan in older patients with atrial septal defect and mild pulmonary vascular disease to decrease pulmonary vascular resistance as assessed by bicycle exercise echocardiography. ;Secondary Objective: To prospectively assess the efficacy of bosentan treatment on cardiopulmonary exercise test parameters, such as peak oxygen consumption (vO2max), oxygen uptake efficiency slope, ventilator efficiency and peak oxygen pulse. To prospectively investigate the effect of bosentan treatment on echocardiographic (two-dimensional, real-time three dimensional, Doppler, Tissue Doppler imaging, 2D speckle tracking ) parameters of right ventricular function. To investigate physiological information provided by CPET in order to elucidate underlying pathophysiological changes in patients with ASD before and after treatment with bosentan. To investigate changes in hemodynamic parameters provided by echocardiograghy in order to elucidate underlying hemodynamic changes and RV function in patients with ASD before and after treatment with bosentan. ;Primary end point(s): Decrease in pulmonary vascular resistance as assessed with bicycle stress echocardiography | — |
Countries
Belgium
Outcome results
None listed