E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003664 |
E.1.2 | Term | Atrial septal defect |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10037400 |
E.1.2 | Term | Pulmonary hypertension |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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.
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E.2.2 | Secondary objectives of the trial |
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.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
Decrease in pulmonary vascular resistance as assessed with bicycle stress echocardiography |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The last visit of the last subject undergoing the trial will be considered the end of trial. In case of an unexpected serious of adverse event, the data safety monitoring board is able to stop the trial.
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |