E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Aortic valve stenosis |
Aortastenose |
|
E.1.1.1 | Medical condition in easily understood language |
Aortic valve narrowing |
Hovedpulsåreklapforsnævring |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10002918 |
E.1.2 | Term | Aortic valve stenosis |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
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 |
3.1 Primary objectives
1. In a consecutive population of patients with mild-moderate AS to compare
a. the rate of progression of peak aortic velocity (m/s) assessed by echocardiography
b. the rate of progression of aortic valve calcification (AU) assessed by non-contrast CT
after 24 months treatment with losartan compared with placebo.
|
|
E.2.2 | Secondary objectives of the trial |
3.2 Secondary objectives
1. In a consecutive population of patients with mild-moderate AS to compare
a. LV geometry and mass (relative wall-thickness, LV mass index) assessed by echocardiography and magnetic resonance imaging.
b. Diastolic function assessed by echocardiography
c. Systolic function (LV ejection fraction, global longitudinal strain) assessed by echocardiography
c. Markers of LV filling pressures (E/e’, NT-proBNP)
after 24 months treatment with losartan compared with placebo treatment.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients with mild-moderate AS (peak aortic jet velocity ≥2.5 and <4m/s)
2. Age >20 years ≤ 85 years
3. LV ejection fraction ≥50%
4. Systolic blood pressure ≥1 00 mmHg
5. Signed informed consent
|
|
E.4 | Principal exclusion criteria |
1. More than mild aortic or mitral regurgitation or mitral stenosis
2. Current use of renin-angiotensin system medication (ACE-I, ARB or
direct renin inhibitor) in patients with arterial hypertension and diabetes
mellitus or arterial hypertension and chronic kidney disease stage 4-5
(estimated glomerular filtration rate <30ml/min/1.73m2)
3. Known allergy or intolerance to ARBs, poorly controlled blood
pressure
4. Renal dysfunction (estimated glomerular filtration
rate <30ml/min/1.73m2), chronic hyperkalemia (P-potassium >5.5
mmol/L)
5. Hepatic failure, cirrhosis, hepatitis or history of hepatic impairment
6. Newly diagnosed (<2 months) or poorly controlled diabetes
7. Pre-existing obstructive coronary artery disease with CCS III-IV
angina or recent myocardial infarction (<3 months)
8. Pregnant or lactating women. Fertile women without highly effective
birth control method. Patients unable to read, understand or sign
research consent |
|
E.5 End points |
E.5.1 | Primary end point(s) |
a. the rate of progression of peak aortic velocity (m/s) assessed by echocardiography
b. the rate of progression of aortic valve calcification (AU) assessed by non-contrast CT
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
a. LV geometry and mass (relative wall-thickness, LV mass index) assessed by echocardiography and magnetic resonance imaging.
b. Diastolic function assessed by echocardiography
c. Systolic function (LV ejection fraction, global longitudinal strain) assessed by echocardiography
c. Markers of LV filling pressures (E/e’, NT-proBNP)
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 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 | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
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
|
LVLS |
hyperkalemia
nyresvigt
hypotension |
|
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 |