Study to Reduce Symptoms of Premature Beats With Ranolazine

NCT ID: NCT01996618

Last Updated: 2015-05-01

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2016-07-31

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.

Conditions

Premature Ventricular Beats

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Ranolazine

Intervention Type: DRUG

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.

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.

Group Type: PLACEBO_COMPARATOR

No interventions assigned to this group

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Ranexa

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Walter Reed National Military Medical Center

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael S Cahill, MD

Role: PRINCIPAL_INVESTIGATOR

Walter Reed National Military Medical Center

Locations

Walter Reed National Military Medical Center

Bethesda, Maryland, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Michael S Cahill, MD

Role: CONTACT

michael.s.cahill.mil@health.mil

301-295-0394

Carin J Smith, MD

Role: CONTACT

carin.j.smith.mil@health.mil

301-295-0394

Facility Contacts

Michael S Cahill, MD

Role: primary

michael.s.cahill.mil@health.mil

301-295-0394

References

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.

Reference Type: BACKGROUND

PMID: 20345626 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19444092 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18439620 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19366821 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18479333 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18598958 (View on PubMed)

Other Identifiers

20043-7

Identifier Type: -

Identifier Source: org_study_id