Clinical trial NCT01996618: Study to Reduce Symptoms of Premature Beats With Ranolazine
Official title: Reduction of Symptomatic Ventricular Premature Beats With Ranolazine
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Premature Ventricular Beats
Keywords: Premature Ventricular Beats
Premature Heart Beats
Ranolazine
Lead sponsor: Walter Reed National Military Medical Center
Sponsor class: FED
First posted: 2013-11-27
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Reduction in Premature Ventricular Beats
timeFrame: 24-hour Holter Monitor after 14 days of therapy
Secondary outcomes:
measure: Changes in transthoracic echocardiographic parameters
timeFrame: 14 days of therapy
measure: Frequency of palpitations
timeFrame: 14 days of therapy
measure: Reduction of Premature Atrial Beats
timeFrame: 24-hour Holter Monitor after 14 days of therapy
measure: Measure Temperature Rebound Rate (TRR)
timeFrame: 14 days of therapy
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: Walter Reed National Military Medical Center
state: Maryland
Study officials:
affiliation: Walter Reed National Military Medical Center
name: Michael S Cahill, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nanda S, Levin V, Martinez MW, Freudenberger R. Ranolazine--treatment of ventricular tachycardia and symptomatic ventricular premature beats in ischemic cardiomyopathy. Pacing Clin Electrophysiol. 2010 Dec;33(12):e119-20. doi: 10.1111/j.1540-8159.2010.02733.x.
citation: Deshmukh SH, Patel SR, Pinassi E, Mindrescu C, Hermance EV, Infantino MN, Coppola JT, Staniloae CS. Ranolazine improves endothelial function in patients with stable coronary artery disease. Coron Artery Dis. 2009 Aug;20(5):343-7. doi: 10.1097/MCA.0b013e32832a198b.
citation: Sossalla S, Wagner S, Rasenack EC, Ruff H, Weber SL, Schondube FA, Tirilomis T, Tenderich G, Hasenfuss G, Belardinelli L, Maier LS. Ranolazine improves diastolic dysfunction in isolated myocardium from failing human hearts--role of late sodium current and intracellular ion accumulation. J Mol Cell Cardiol. 2008 Jul;45(1):32-43. doi: 10.1016/j.yjmcc.2008.03.006. Epub 2008 Mar 14.
citation: Gul KM, Ahmadi N, Wang Z, Jamieson C, Nasir K, Metcalfe R, Hecht HS, Hartley CJ, Naghavi M. Digital thermal monitoring of vascular function: a novel tool to improve cardiovascular risk assessment. Vasc Med. 2009 May;14(2):143-8. doi: 10.1177/1358863X08098850.
citation: Kumar K, Nearing BD, Bartoli CR, Kwaku KF, Belardinelli L, Verrier RL. Effect of ranolazine on ventricular vulnerability and defibrillation threshold in the intact porcine heart. J Cardiovasc Electrophysiol. 2008 Oct;19(10):1073-9. doi: 10.1111/j.1540-8167.2008.01204.x. Epub 2008 May 9.
citation: Sicouri S, Glass A, Belardinelli L, Antzelevitch C. Antiarrhythmic effects of ranolazine in canine pulmonary vein sleeve preparations. Heart Rhythm. 2008 Jul;5(7):1019-26. doi: 10.1016/j.hrthm.2008.03.018. Epub 2008 Mar 21.