Premature Ventricular Beats
Conditions
Keywords
Premature Ventricular Beats, Premature Heart Beats, Ranolazine
Brief summary
Investigate whether ranolazine, a novel anti-anginal agent with antiarrhythmic properties, has a role in the management of symptomatic ventricular premature beats.
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.
Interventions
DRUGRanolazine
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.
Sponsors
Walter Reed National Military Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
Countries
United States
Contacts
Primary ContactMichael S Cahill, MD
Backup ContactCarin J Smith, MD
Outcome results
None listed