E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
To study whether bosentan (endothelin receptor inhibitor) improves aerobic capacity (VO2max) and exercise performance in adult patients with a Fontan operation. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064911 |
E.1.2 | Term | Pulmonary arterial hypertension |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To study whether bosentan (endothelin receptor inhibitor) improves aerobic capacity (VO2max) and exercise performance in adult patients with a Fontan operation. |
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E.2.2 | Secondary objectives of the trial |
Change in: a. changes in six-minute-walk-distance b. change in quality of life score c. change in prevalence of arrhythmias d. changes in congestive heart failure (hospital admission, use of medication for congestive heart failure e. changes in prevalence of protein losing enteropathy f. changes in serum of neurohormones level (NT-pro BNP, endothelin-1) g. changes in cardiac output h changes in arterial oxygen saturation i. changes in number of deaths
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All adult Fontan patients are potentially eligible for this study. |
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E.4 | Principal exclusion criteria |
Patients are not eligible for this study if the following inclusion criteria apply: - Systemic arterial pressure < 85 mmHg - Incapable of giving informed consent - Hypersensitivity to bosentan or any of its help substances - Current treatment with bosentan or treatment for pulmonary arterial hypertension - Moderate to severe liver disease: Child-Pugh class B or C - Raised plasma transaminases level > three times limiting value. - Simultaneous use of cyclosporine A - Pregnant or nursing women (a pregnancy test is offered to every female patient within the fertile age) - Desire to have children within the study period or women who do not use reliable contraceptive methods |
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E.5 End points |
E.5.1 | Primary end point(s) |
change in aerobic capacity.
Sample size calculation is based on the primary endpoint change in aerobic capacity (percentage of predicted VO2max). Giardini et al (2008) found a mean improvement in peak V’O2 of 1.9 ml/kg/min (change 9.% ± 5.2%) after treatment with sildenafil in 18 patients with a Fontan circulation (78% total cavo-pulmonary connection).6 Based on a standard deviation of 1.89 we calculated that 32 patients are required to obtain 80% power to detect a difference in mean percentage of peak VO2 2.0 ml/kg/min between the two groups after 12 weeks with a 2 sided α of 0.05. To accommodate for a 10% drop out, the inclusion of at least 40 patients is advised. According to the CONCOR database, the capacity of our study centres meets this criterion |
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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 | Yes |
E.6.4 | Safety | Yes |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
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 | No |
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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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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |