Study to Reduce Symptoms of Premature Beats With Ranolazine

Study Overview
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Brief Summary
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Investigate whether ranolazine, a novel anti-anginal agent with antiarrhythmic properties, has a role in the management of symptomatic ventricular premature beats.

Detailed Description
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The main objective is to compare the effect of ranolazine versus placebo on premature ventricular beats (using 24-hour ambulatory electrocardiographic monitoring) for subjects with symptomatic palpitations. Subject population will consist of seventy-two adult subjects of both sexes who have greater than 1,000 premature ventricular beats during initial monitoring.

Official Title
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Reduction of Symptomatic Ventricular Premature Beats With Ranolazine

Conditions
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Premature Ventricular Beats

Intervention / Treatment
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* Drug: Ranolazine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects male and female 18 years and older Symptoms of palpitations Greater than or equal to 1,000 Ventricular Premature Beats during 24-hour electrocardiographic monitoring Completion of a consent form prior to pre-randomization Holter monitor Exclusion Criteria: Moderate to severe symptomatic heart failure, New York Heart Association Class III/IV Moderate to severe symptomatic angina, Canadian Cardiovascular Classification III/IV Moderate to severe structural heart disease in the absence of an implantable cardiac defibrillator in a subject who would otherwise be eligible for a defibrillator (e.g. history of myocardial infarction and a left ventricular ejection fraction less than 30%) Clinically significant hepatic disease (cirrhosis or chronic hepatitis) or abnormal liver associated enzymes greater than three times the upper limits of normal A baseline corrected QT interval greater than or equal to 500msec or history of congenital channelopathy (long QT syndrome, Brugada syndrome) or torsades de pointes. Treatment with agents known to prolong the QTc interval Treatment with agents that are potent or moderately potent inhibitors of CYP3A, to include, but is not limited to the following: ketoconazole, HIV protease inhibitors (i.e. ritonavir), macrolide antibiotics (i.e. clarithromycin), diltiazem and verapamil Females who are pregnant, planning to get pregnant, or breast feeding ( females under the age of 55 years who have not previously undergone surgical sterilization procedures will have serum qualitative pregnancy testing) Thyroid stimulating hormone less than 0.27 IU/mL Serum magnesium less than 1.5mg/dL Serum potassium less than 3.5 mEq/dL or greater than 5.0 mEq/dL Estimated GFR less than 30 mL/min

Ages Eligible for Study
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Minimum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ranolazine<br>Subjects will be consented by the study investigator and then randomly assigned in an allocation-concealed fashion to double blinded treatment with either titrated doses of ranolazine or matched placebo. After the initial 6 days of treatment with ranolazine, 500 mg twice daily or matched placebo, subjects will undergo repeat 24 hour electrocardiographic monitoring. If tolerated, the subjects will then have their study medication increased (Ranolazine 1,000 mg twice daily or matching placebo) with the plan to then undergo a repeat 24 hour ambulatory electrocardiographic monitoring in 6 days. When the subject returns the monitor, subjects will enter the washout period (cessation of the study medication) for 6 days and have electrocardiographic monitoring prior to return to the subject's referring provider for care. | Drug: Ranolazine<br>* After the initial 6 days of treatment with ranolazine, 500 mg twice daily or matched placebo, subjects will undergo repeat 24 hour electrocardiographic monitoring. If tolerated, the subjects will then have their study medication increased (Ranolazine 1,000 mg twice daily) with the plan to then undergo a repeat 24 hour ambulatory electrocardiographic monitoring in 6 days.<br>* Other names: Ranexa;|
| Placebo Comparator: Placebo<br>Subjects will be consented by the study investigator and then randomly assigned in an allocation-concealed fashion to double-blinded treatment with either titrated doses of ranolazine or matched placebo. After the initial 6 days of treatment with ranolazine, 500 mg twice daily or matched placebo, subjects will undergo repeat 24 hour electrocardiographic monitoring. If tolerated, the subjects will then have their study medication increased (Ranolazine 1,000 mg twice daily or matching placebo) with the plan to then undergo a repeat 24-hour ambulatory electrocardiographic monitoring in 6 days. When the subject returns the monitor, subjects will enter the washout period (cessation of the study medication) for 6 days and have electrocardiographic monitoring prior to return to the subject's referring provider for care. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in Premature Ventricular Beats | The primary endpoint will be a 50% reduction in premature ventricular beats during 24-hour Holter monitoring after randomization to active treatment or placebo for 14 days of therapy. | 24-hour Holter Monitor after 14 days of therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in transthoracic echocardiographic parameters | Measure changes in transthoracic echocardiographic parameters including diastolic parameters, mitral inflow velocities and deceleration time and mitral annular velocities using tissue doppler imaging. | 14 days of therapy | 
| Frequency of palpitations | Patient perceived change in frequency of palpitations from baseline to follow-up visit. | 14 days of therapy | 
| Reduction of Premature Atrial Beats | Reduction of premature atrial beats during 24-hour holter monitoring after randomization to active treatment or placebo following 14 days of therapy. | 24-hour Holter Monitor after 14 days of therapy | 
| Measure Temperature Rebound Rate (TRR) | Measure serial change in endothelial function as measured using the Vendys® DTM device as measured by fingertip Temperature Rebound (TR) in degrees Celsius. Temperature rebound is measured as the absolute difference between low fingertip temperature during cuff occlusion and maximal temperature rebound following cuff release. In addition, rate of change (slope) in temperature rebound will be calculated, measured as the TR divided by the time from temperature nadir to temperature peak. This will be termed: temperature rebound rate (TRR). | 14 days of therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Premature Ventricular Beats, Premature Heart Beats, Ranolazine