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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified November 2013 by Walter Reed National Military Medical Center
Sponsor:
Information provided by (Responsible Party):
Walter Reed National Military Medical Center
ClinicalTrials.gov Identifier:
NCT01996618
First received: November 21, 2013
Last updated: NA
Last verified: November 2013
History: No changes posted
  Purpose

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


Condition Intervention Phase
Premature Ventricular Beats
Drug: Ranolazine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Reduction of Symptomatic Ventricular Premature Beats With Ranolazine

Resource links provided by NLM:


Further study details as provided by Walter Reed National Military Medical Center:

Primary Outcome Measures:
  • Reduction in Premature Ventricular Beats [ Time Frame: 24-hour Holter Monitor after 14 days of therapy ] [ Designated as safety issue: No ]
    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 [ Time Frame: 14 days of therapy ] [ Designated as safety issue: No ]
    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 [ Time Frame: 14 days of therapy ] [ Designated as safety issue: No ]
    Patient perceived change in frequency of palpitations from baseline to follow-up visit.

  • Reduction of Premature Atrial Beats [ Time Frame: 24-hour Holter Monitor after 14 days of therapy ] [ Designated as safety issue: No ]
    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) [ Time Frame: 14 days of therapy ] [ Designated as safety issue: No ]
    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).


Estimated Enrollment: 72
Study Start Date: January 2014
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01996618

Contacts
Contact: Michael S Cahill, MD 301-295-0394 michael.s.cahill.mil@health.mil
Contact: Carin J Smith, MD 301-295-0394 carin.j.smith.mil@health.mil

Locations
United States, Maryland
Walter Reed National Military Medical Center Not yet recruiting
Bethesda, Maryland, United States, 20889
Contact: Michael S Cahill, MD    301-295-0394    michael.s.cahill.mil@health.mil   
Principal Investigator: Michael S Cahill, MD         
Sponsors and Collaborators
Walter Reed National Military Medical Center
Investigators
Principal Investigator: Michael S Cahill, MD Walter Reed National Military Medical Center
  More Information

Publications:

Responsible Party: Walter Reed National Military Medical Center
ClinicalTrials.gov Identifier: NCT01996618     History of Changes
Other Study ID Numbers: 20043-7
Study First Received: November 21, 2013
Last Updated: November 21, 2013
Health Authority: United States: Federal Government

Keywords provided by Walter Reed National Military Medical Center:
Premature Ventricular Beats
Premature Heart Beats
Ranolazine

Additional relevant MeSH terms:
Cardiac Complexes, Premature
Ventricular Premature Complexes
Arrhythmias, Cardiac
Cardiovascular Diseases
Heart Diseases
Pathologic Processes
Ranolazine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 23, 2014