RSVP: Study to Reduce Symptoms of Premature Beats With Ranolazine

Sponsor

Walter Reed National Military Medical Center (U.S. Fed)

Overall Status

Unknown status

CT.gov ID

NCT01996618

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

2.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Premature Ventricular Beats	Drug: Ranolazine	Phase 4

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

72 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

Reduction of Symptomatic Ventricular Premature Beats With Ranolazine

Study Start Date :

Jan 1, 2014

Anticipated Primary Completion Date :

Jun 1, 2016

Anticipated Study Completion Date :

Jul 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ranolazine 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 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. Other Names: Ranexa
Placebo Comparator: Placebo 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.

Arm

Intervention/Treatment

Experimental: Ranolazine

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

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.

Other Names:

Ranexa

Placebo Comparator: Placebo

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.

Outcome Measures

Primary Outcome Measures

Reduction in Premature Ventricular Beats [24-hour Holter Monitor after 14 days of therapy]
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.

Secondary Outcome Measures

Changes in transthoracic echocardiographic parameters [14 days of therapy]
Measure changes in transthoracic echocardiographic parameters including diastolic parameters, mitral inflow velocities and deceleration time and mitral annular velocities using tissue doppler imaging.
Frequency of palpitations [14 days of therapy]
Patient perceived change in frequency of palpitations from baseline to follow-up visit.
Reduction of Premature Atrial Beats [24-hour Holter Monitor after 14 days of therapy]
Reduction of premature atrial beats during 24-hour holter monitoring after randomization to active treatment or placebo following 14 days of therapy.
Measure Temperature Rebound Rate (TRR) [14 days of therapy]
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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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