E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Aortic stenosis of at least moderate degree (peak velocity >=3.0m/sec or aortic valve area <1.5cm2) |
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MedDRA Classification |
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 examine the regression of LV mass and changes in left ventricular (LV) physiological parameters using Cardiac Magnetic Resonance (CMR) and magnetic resonance spectroscopy (MRS) in patients with moderate to severe aortic stenosis treated with the angiotensin converting enzyme (ACE) inhibitor ramipril. |
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E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability of ramipril in asymptomatic patients with moderate to severe aortic stenosis. To examine potential improvement in effort tolerance as assessed by exercise treadmill testing (ETT).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male or Female, aged 18 years or above. • Diagnosed with asymptomatic aortic stenosis of at least moderate degree (peak velocity >3.0m/sec; gradient >36mmHg or valve area <1.5cm2 by echocardiography) for whom aortic valve replacement surgery is currently not contemplated. • Left ventricular ejection fraction on echocardiography >=40% without regional wall motion abnormality suggestive of significant previous myocardial infarction. • Patient or legal representative is willing and able to give informed consent for participation in the study. • Able (in the Investigators opinion) and willing to comply with all study requirements.
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E.4 | Principal exclusion criteria |
• Other significant valve disease • Female who is pregnant, lactating or planning pregnancy during the course of the study. • Significant renal impairment (estimated GFR<30mls/minute). If moderate renal impairment is present (GFR 30-59mls/minute), patients may be included in the study, but will not receive gadolinium contrast during the CMR scan • Known hepatic impairment (AST/ALT > 2 times the upper limit of normal). • Prescription of ACE inhibitors or angiotensin II receptor blockers (ARBs) within the 3 months prior to the start of the study • Past history of an allergic reaction or intolerance to ACE inhibitors. • Sustained systolic blood pressure <100mmHg or >200mmHg or diastolic blood pressure <40mmHg or >110mmHg at baseline measurement. • Contraindication to magnetic resonance scanning (pacemaker, cranial aneurysm clips, metallic ocular foreign bodies, severe claustrophobia). • Patient is terminally ill. • Any other significant disease or disorder which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, or may influence the result of the study, or the patient ability to participate in the study. • Patient/subjects who have participated in another research study involving an investigational product in the past 3 months. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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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 | No |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | No |
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 | 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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The date of the last follow up contact of the last patient. |
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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 | 2 |
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 | 2 |
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 |