E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Heart failure with preserved ejection fraction (HFpEF) |
|
E.1.1.1 | Medical condition in easily understood language |
Diastolic heart failure |
Diastolisch hartfalen |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
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 |
Assess the effect of a 3-month trimetazidine treatment in patients with HFpEF on LV diastology (change in exercise PCWP measured by exercise right heart catheterization or RHC) |
|
E.2.2 | Secondary objectives of the trial |
Assess the effect of a 3-month trimetazidine treatment in patients with HFpEF on myocardial energy content (PCr/ATP-ratio measured by 31P-MR spectroscopy) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
In order to be eligible to participate in this study, a subject must meet all of the following criteria:
1. Diagnosis of HFpEF:
a. signs/and or symptoms of heart failure, NYHA II or higher (and ambulant)
b. LVEF ≥ 50% (by any modality)
c. evidence of LV diastolic dysfunction (PCWP at rest >15mmHg and/or PCWP during exercise ≥ 25mmHg; diastolic dysfunction grade II or higher with a NT-proBNP level >125 pg/mL) [1,23,32]
d. no other significant cardiac (e.g. significant valvular disease) or extra-cardiac condition (e.g. severe COPD) that explains symptoms
2. Clinically stable (no change in diuretic for >1 month), co-morbidities managed
3. Informed consent |
|
E.4 | Principal exclusion criteria |
1. Current acute decompensated heart failure, requiring augmented therapy with intravenous diuretics, vasodilator and/or inotropic drugs;
2. Acute coronary syndrome, TIA/CVA, major surgery within the 3 months prior;
3. Suspected septal scar (e.g. due to myocardial infarction) which prohibits the measurement of PCr/ATP ratio with MRS;
4. Unable to undergo the complete study protocol (RHC, MRI/MRS, 6MWD);
5. Contra-indication for trimetazidine (severe kidney failure with an eGFR <30ml/min, parkinsonism or patients requiring medication that cause parkinsonism);
6. Doubt about compliance;
7. Pre-menopausal women who are nursing, pregnant, or of child-bearing potential and not practicing an acceptable method of birth control;
8. Chronic absorption problems
9. Estimated life-expectancy < 1 year.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Exercise PCWP measured by RHC (gold standard for the evaluation of LV diastology) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Myocardial PCr/ATP-ratio measured by 31P-MRS |
|
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 | 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 | Yes |
E.6.13.1 | Other scope of the trial description |
|
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 | Yes |
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 | 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 | No |
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
|
End of trial: last visit of last subject |
|
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 | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |