Health Condition 1: I503- Diastolic (congestive) heart failure
Conditions
Interventions
Intervention1: Ranolazine: Tablet Ranolazine 500 mg twice daily orally for 24 weeks
Control Intervention1: Placebo: Placebo twice daily for 24 weeks
Sponsors
Indian Council of Medical Research ICMR
Eligibility
Inclusion criteria
Inclusion criteria: (All should be satisfied) 1. Patients have diagnosis of symptomatic heart failure with Left Ventricular Ejection Fraction (LVEF) > 45%. 2. Plasma level of NT-proBNP >300 ng/mL 3. NYHA class II to IV heart failure 4. Age � 18 years of either sex.
Exclusion criteria
Exclusion criteria: 1. Patients already on treatment with ranolazine or have been administered with ranolazine within past 24 weeks. 2. Patients with Acute Coronary Syndrome, cardiac surgery within period of last 24 weeks. 3. Patients receiving concomitant strong CYP3A4 inhibitor (e.g. diltiazem, verapamil) or inducer (e.g., rifampicin, carbamazepine). 4. Patients who are taking concomitant P glycoprotein inhibitor (e.g cyclosporine). 5. Patients who have participated in another trial in the past 3 months. 6. Patients with history of cardiac arrhythmia or is currently undertaking treatment with antiarrhythmic drugs 7. Anaemia (Hb 8. HbA1c >8 g%, (for inclusion of diabetes patients) 9. Pregnancy and lactating mothers 10. not willing to follow contraceptive measures if in reproductive age group 11. Cirrhosis 12. Age > 75 years ( to have upper cut off for age as Ranolazine related ADRs are more in elderly) 13. HR 14. Patients with history, signs and symptoms suggestive of pericardial constriction, cor pulmonale, implanted pacemaker, implanted LVAD, implanted cardioverter - defibrillator, significant pulmonary disease (requiring active treatment with oxygen and steroid), valvular heart disease, acute decompensated heart failure. 16. Patients with congenital or acquired QT interval prolongation, familial history of QT interval prolongation, QTc interval of >450 ms in males and >470 ms in Females. 17. Patients with history of Myocardial infarction, CABG surgeryand PCI in the previous 6 month. 18. Patients with history of uncontrolled hypertension (blood pressure that is inadequately treated rather than blood pressure that is resistant to treatment, as might be observed with secondary causes of hypertension such as renal artery stenosis). 19. Patients with history of valvular heart disease. 20. Patients with significant pulmonary disease, COPD. 21. Patients who have osteoarthritis or any other conditions which would prevent him/her from performing 6 minute walk test 22. Patients with renal creatinine clearance � 30 ml/min (Cockcroft - Gault formula) or with severe hepatic impairment (Child Pugh class B or Class C). 23. Patients who are not willing for follow up at the participating institute for a period of 6 months.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Change from baseline in 6-minute walk distance (6MWD) at Week 24. 2. Change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS) at Week 24. Timepoint: Baseline, 12 weeks, 24 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| iv. Change in echocardiographic parameters at baseline,12 weeks and 24 weeks. a. Left Ventricular End Diastolic Volume (LVEDV in ml) b. Left Ventricular End Diastolic Volume Index (LVEDVI in ml/kg) c. Left Ventricular End Systolic Volume (LVESV in ml) d. Left Ventricular End Systolic Volume Index(LVESVI in ml/kg) e. Left Ventricular Stroke Volume (LVSV in ml) f. Left Ventricular Ejection Fraction (LVEF in %) g. Mitral E wave velocity (E in cm/s) h. Mitral A wave velocity (A in cm/s) i. Mitral E/A wave velocity (E/A) j. Mitral annular velocity (Eââ?¬â?¢ in cm/s) k. Mitral wave velocity / Mitral annular velocity (E/Eââ?¬â?¢) l. Peak atrial longitudinal strain Timepoint: Baseline, 12 weeks, 24 weeks;v. Change in concentration of NT-proBNP measured at baseline, 12 weeks, 24 weeksTimepoint: Baseline, 12 weeks, 24 weeks;vi. Days of hospitalisation due to heart failure at 24 weeks.Timepoint: Baseline, 12 weeks, 24 weeks;vii. Change in baseline score of NYHA class (New York Heart Association) at baseline, 12 weeks, 24 weeks.Timepoint: Baseline, 12 weeks, 24 weeks;viii. Frequency of adverse eventsTimepoint: Baseline, Day-15, Day-45, Day-90, Day-120, Day-150, Day-180 ;i. Composite of CV death, total HF hospitalizations, total non-fatal strokes and total non-fatal myocardial infarction over a period of 24 weeks.Timepoint: Baseline, 12 weeks, 24 weeks;ii. Percentage of Patients With 5-points or more improvement in KCCQ Clinical Summary Score(CSS) at Week 24Timepoint: Baseline, 12 weeks, 24 weeks;iii. Percentage of Patients With 10-points or more improvement in KCCQ CSS at Week 24Timepoint: Baseline, 12 weeks, 24 weeks | — |
Countries
India
Contacts
Public ContactSamir Malhotra
PGIMER Chandigarh
Outcome results
None listed