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Study to Reduce Symptoms of Premature Beats With Ranolazine (RSVP)

Primary Purpose

Premature Ventricular Beats

Status
Unknown status
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Ranolazine
Sponsored by
Walter Reed National Military Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Premature Ventricular Beats focused on measuring Premature Ventricular Beats, Premature Heart Beats, Ranolazine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Walter Reed National Military Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Ranolazine

Placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Frequency of palpitations
Patient perceived change in frequency of palpitations from baseline to follow-up visit.
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.
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).

Full Information

First Posted
November 21, 2013
Last Updated
April 30, 2015
Sponsor
Walter Reed National Military Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT01996618
Brief Title
Study to Reduce Symptoms of Premature Beats With Ranolazine
Acronym
RSVP
Official Title
Reduction of Symptomatic Ventricular Premature Beats With Ranolazine
Study Type
Interventional

2. Study Status

Record Verification Date
November 2013
Overall Recruitment Status
Unknown status
Study Start Date
January 2014 (undefined)
Primary Completion Date
June 2016 (Anticipated)
Study Completion Date
July 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Walter Reed National Military Medical Center

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Premature Ventricular Beats
Keywords
Premature Ventricular Beats, Premature Heart Beats, Ranolazine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
72 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ranolazine
Arm Type
Experimental
Arm Description
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 Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Ranolazine
Other Intervention Name(s)
Ranexa
Intervention Description
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.
Primary Outcome Measure Information:
Title
Reduction in Premature Ventricular Beats
Description
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.
Time Frame
24-hour Holter Monitor after 14 days of therapy
Secondary Outcome Measure Information:
Title
Changes in transthoracic echocardiographic parameters
Description
Measure changes in transthoracic echocardiographic parameters including diastolic parameters, mitral inflow velocities and deceleration time and mitral annular velocities using tissue doppler imaging.
Time Frame
14 days of therapy
Title
Frequency of palpitations
Description
Patient perceived change in frequency of palpitations from baseline to follow-up visit.
Time Frame
14 days of therapy
Title
Reduction of Premature Atrial Beats
Description
Reduction of premature atrial beats during 24-hour holter monitoring after randomization to active treatment or placebo following 14 days of therapy.
Time Frame
24-hour Holter Monitor after 14 days of therapy
Title
Measure Temperature Rebound Rate (TRR)
Description
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).
Time Frame
14 days of therapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Michael S Cahill, MD
Phone
301-295-0394
Email
michael.s.cahill.mil@health.mil
First Name & Middle Initial & Last Name or Official Title & Degree
Carin J Smith, MD
Phone
301-295-0394
Email
carin.j.smith.mil@health.mil
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael S Cahill, MD
Organizational Affiliation
Walter Reed National Military Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Walter Reed National Military Medical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20889
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michael S Cahill, MD
Phone
301-295-0394
Email
michael.s.cahill.mil@health.mil
First Name & Middle Initial & Last Name & Degree
Michael S Cahill, MD

12. IPD Sharing Statement

Citations:
PubMed Identifier
20345626
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.
Results Reference
background
PubMed Identifier
19444092
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.
Results Reference
background
PubMed Identifier
18439620
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.
Results Reference
background
PubMed Identifier
19366821
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.
Results Reference
background
PubMed Identifier
18479333
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.
Results Reference
background
PubMed Identifier
18598958
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.
Results Reference
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Study to Reduce Symptoms of Premature Beats With Ranolazine

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