A Pilot Trial of Ranolazine to Treat Patients With Dilated Cardiomyopathy

Study Overview
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Brief Summary
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Recent data suggest that areas of fibrosis and hibernating myocardium develop in patients with non ischemic dilated cardiomyopathy. Ranolazine is a new drug, developed to releave symptoms of angina in patients with stable coronary disease that is not suitable for surgical or percutaneous revascularization. It has been shown that in patients with stable coronary disease Ranolazine improves myocardial perfusion as shown with myocardial nuclear imaging. The aim of this trial is to evaluate effects of ranolazine on myocardial perfusion in patients with dilated cardiomyopathy.

Detailed Description
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Recent data suggest that areas of fibrosis and hibernating myocardium develop in patients with non ischemic dilated cardiomyopathy. Ranolazine is a new drug, developed to releave symptoms of angina in patients with stable coronary disease that is not suitable for surgical or percutaneous revascularization. The main mechanism of action of Ranolazine is the inhibition of late I(Na) thus decreasing the Ca++ load in the cardiomyocites. Consequently oxygen consumption also decreases. It has also been shown that in patients with stable coronary disease Ranolazine improves myocardial perfusion as shown with myocardial nuclear imaging. The aim of this trial is to evaluate effects of ranolazine on myocardial perfusion in patients with dilated cardiomyopathy. Primary end-point: To determine wheather Ranolazine improves perfusion of the myocardium in patients with non-ischemic dilated cardiomyopathy. Secondary end-points: To determine wheather Ranolazine improves patients' NYHA functional class, excercise capacity, LV systolic and diastolic function and weather ranolazine affects supraventricular and ventricular arrhythmia occurance/frequency.

Official Title
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Effects of Ranolazine on Myocardial Perfusion in Patients With Dilated Cardiomyopathy

Conditions
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Dilated Cardiomyopathy

Intervention / Treatment
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* Drug: Ranolazine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: established diagnosis of non-ischemic dilated cardiomyopathy EF < 35% NYHA f.c. II - IV Optimal medical management > 6 months Age < 75 years and > 18 years Exclusion Criteria: known hypersensitivity to the medication age > 75 years or < 18 years EF > 35% renal insufficiency (GF < 30) liver dysfunction (liver tests > 3x the upper normal limit)) LQT syndrome drugs that affect CYP3A4 metabolism (azoles, macrolides, calcineurin inhibitors etc.) dementia active hemathological or malignant disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Controls<br> | |
| Experimental: Ranolazine<br>Initial dose is 375 mg bid. After 2 - 4 weeks the dose is increased to 500 mg bid and after another 2-4 weeks to 750 mg bid. In case of side effects the dose of the drug is to be decreased to the highest dose that the patient is still able to tolerate. | Drug: Ranolazine<br> <br> * Other names: Ranexa;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial perfusion | To determine wheather Ranolazine improves perfusion of the myocardium in patients with non-ischemic dilated cardiomyopathy assesed by myocardial nuclear imaging. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Excercise capacity | To determine wheather Ranolazine improves patients' excercise capacity, assesed by 6' walk test | 1, 3 and 6 months | 
| Left ventricular systolic and diastolic function | To determine wheather Ranolazine improves patients' LV systolic and diastolic function, assesed by LVEF, TDI, LV longitudinal strain and strain rate | 1, 3 and 6 months | 
| Supraventricular and ventricular arrhythmias | To determine wheather Ranolazine affects the occurence of supraventricular and ventricular arrhythmia occurance/frequency using 24 holter monitor. | 6 months |