No registrations found.
ID
Source
Brief title
Health condition
Heart failure with preserved ejection fraction
Sponsors and support
Intervention
Outcome measures
Primary outcome
Exercise pulmonary capillary wedge pressure (PCWP) measured by right heart catheterisation
Secondary outcome
Key secondary endpoint: myocardial PCr/ATP-ratio measured by 31P-MRS;
Safety endpoint: (S)AE; Metabolic: trimetazidine plasma levels, mitochondrial function, insulin resistance (HOMA); Exploratory: NT-proBNP, 6MWD, quality-of-life (KCCQ, EQ-5D).
Background summary
Rationale: currently, no treatment exists for heart failure with preserved ejection fraction (HFpEF) (except diuretics and exercise). Heart failure with preserved ejection fraction is associated with lowered cardiac energy levels, furthermore left ventricular relaxation is a highly energy-consuming process (comparable to stretching of a spring). We hypothesize that trimetazidine (a fatty acid oxidation inhibitor) improves left ventricular diastolic dysfunction in HFpEF, by improving mitochondrial function and increasing myocardial energy content.
Main objective: assess whether: trimetazidine treatment 1) improves LV diastology; 2) improves LV myocardial energy content in HFpEF.
Study design: double-blind placebo-controlled cross-over intervention study.
Study population: patients with stable HFpEF: 1) signs and/or symptoms of heart failure; 2) LVEF >50%; 3) evidence of left ventricular diastolic dysfunction; with the exclusion of other significant co-morbidity (especially other severe cardiac conditions, severe kidney failure, parkinsonism) and able to comply the complete protocol (RHC, MRI/MRS).
Intervention: Trimetazidine tablet 20mg TID (BID if eGFR 30-60 ml/min) or placebo for 2 times 3 months with a 2-week washout period.
Main study parameters/endpoints: Primary endpoint: exercise pulmonary capillary wedge pressure (PCWP) measured by right heart catheterization (RHC);
Key secondary endpoint: myocardial PCr/ATP-ratio measured by 31-phosphorus-magnetic resonance spectroscopy;
Safety endpoint: (S)AE; Metabolic: trimetazidine plasma levels, mitochondrial function, insulin resistance (HOMA); Exploratory: NT-proBNP, 6-Minute-Walk-Distance (6-MWD), quality-of-life (KCCQ, EQ-5D).
Study objective
We hypothesize that trimetazidine improves left ventricular diastolic dysfunction in HFpEF, by improving mitochondrial function and increasing myocardial energy content
Study design
9
Intervention
Trimetazidine tablet 20mg TID (BID if eGFR 30-60 ml/min) or placebo for 2 times 3 months with a 2-week washout period.
Inclusion criteria
1. Diagnosis of Heart failure with preserved ejection fraction (HFpEF):
a) signs/and or symptoms of heart failure, NYHA II or higher (and ambulant).
b) LVEF >50%
c) evidence of LV diastolic dysfunction; with the exclusion of other significant co-morbidity (especially other severe cardiac conditions, severe kidney failure, parkinsonism) and able to comply the complete protocol (RHC, MRI/MRS).
d. no other significant cardiac (e.g. significant valvular disease) or extra-cardiac condtion (e.g. severe COPD) that explains symptoms.
2. Clinically stable (no change in diuretics >1 month), co-morbidities managed.
3. Informed consent.
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 with magnetic resonance spectroscopy (MRS))
4. Unable to undergo the complete study protocol (right heart catheterization, MRI/MRS, 6-MWD)
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.
Design
Recruitment
IPD sharing statement
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL7830 |
| Other | METC VUMC / CCMO : METC2018.370 |