Effect of Ranolazine on Arrhythmias and Microvolt T- Wave Alternans (MVTWA) Patients With LV Dysfunction

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Karen Olson, Aspirus Heart and Vascular Institute-Research and Education
ClinicalTrials.gov Identifier:
NCT00998218
First received: October 16, 2009
Last updated: February 8, 2012
Last verified: February 2012
  Purpose

The purpose this investigation is to more thoroughly investigate the effects of ranolazine on arrhythmias and microvolt t-wave alternans in patients who have an automatic implantable cardioverter defibrillator (AICD) implanted either prophylactically to prevent sudden cardiac death, as well as in patients who may have had a clinically significant arrhythmic event prompting the insertion of the automatic implantable cardioverter defibrillator. It is anticipated this study will provide valuable new insight into the potential use of ranolazine to treat arrhythmias in higher risk patients.


Condition Intervention Phase
Sudden Cardiac Death
Ventricular Arrythmias
Drug: Ranolazine
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effect of Ranolazine on Cardiac Arrhythmias and Microvolt T- Wave Alternans in Patients With Significant Left Ventricular Dysfunction

Resource links provided by NLM:


Further study details as provided by Aspirus Heart and Vascular Institute-Research and Education:

Primary Outcome Measures:
  • The effect of ranolazine compared to placebo on MVTWA and reproducibility of MVTWA will be demonstrated. A p value of < 0.05 will be considered significant [ Time Frame: After 4 weeks of treatment ] [ Designated as safety issue: No ]

Enrollment: 7
Study Start Date: September 2009
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ranolazine
Ranolazine at 1000 mg BID (or 500 mg BID if the 1000 mg dose was not tolerated) for 4 weeks
Drug: Ranolazine
Ranolazine at 1000 mg BID (or 500 mg BID if the 1000 mg dose was not tolerated) or a comparable placebo for the next 4 weeks
Placebo Comparator: Sugar pill
Placebo comparator BID for 4 weeks.
Drug: Placebo
Ranolazine at 1000 mg BID (or 500 mg BID if the 1000 mg dose was not tolerated) or a comparable placebo for the next 4 weeks

Detailed Description:

The device clinic of Aspirus Wausau Hospital follows approximately 2800 patients with pacemakers and automatic implantable cardioverter defibrillators (AICD). Approximately 300 of these patients have had an AICD inserted for primary or secondary arrhythmia prevention. From these 300 patients, approximately 20 patients who have an AICD implanted either prophylactically or for an established malignant arrhythmia will be recruited for this short study.

This is a study to investigate the effect of ranolazine on arrhythmias detected by their device to see if it will reduce abnormal beats. It will also study whether ranolazine will impact microvolt t-wave alternans (MVTWA), a measure of the tendency to have a serious arrhythmia. Approximately 10 patients with ischemic cardiomyopathy and 10 patients with a non-ischemic cardiomyopathy will be chosen. All will have an ejection fraction of 40% or less. Prior to institution of ranolazine, a MVTWA study will be performed (Cambridge Heart Inc.®). The AICD will be used to generate the increase in the heart rate needed to induce MVTWA. Each patient will have MVTWA assessed at 80 beats/minute and then again at 110 beats/minute. To eliminate interpretation bias, the auto interpretation feature of the MVTWA device will be used to determine whether the study is positive (MVTWA present) or negative (MVTWA absent) or indeterminate. In the coarse of this study, each patient will undergo a total of 3 MVTWA studies in an identical manner using the AICD to provide the needed changes in heart rate.

After informed consent is obtained the patient will begin a 10-day "ranolazine run in". Each randomized participant will be given a 10-day supply of ranolazine to make certain they tolerate the medication (constipation is by far the most common limiting side effect). Each participant will be started on 500 mg BID and after 3 days increased to 1000 mg BID. Participants able to tolerate at least 500 mg BID will then be considered eligible to participate in the study and randomly assigned to either ranolazine at 1000 mg BID (or 500 mg BID if the 1000 mg dose was not tolerated) or a comparable placebo for the next 4 weeks.

At least 3 days after the run in and prior to randomization, each patient will be brought in for or the baseline MVTWA and the device clinic will purge the AICD of data and reset the data counter. The patient will then immediately begin either placebo or ranolazine according to randomization. After 4 weeks, the MVTWA study will be repeated on either placebo or ranolazine and the arrhythmia data down loaded from the AICD, recorded and the arrhythmia counters and device operation counter again reset. Each patient will then cross over to the other therapy (ranolazine or placebo) for the next 4 weeks and the device interrogated and the MVTWA study repeated in an identical manner.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Implant of AICD for the prevention of sudden cardiac death Implant of AICD for the prevention of sudden cardiac death

Exclusion Criteria:

  • Any anti-arrhythmic agent (other than beta-blockers)
  • History of or intolerance to ranolazine during the run in.
  • History of severe constipation defined as requiring laxatives more than 5 times a week in order to have a bowel movement.
  • Because of a weak inhibitory effect of ranolazine of the cytochrome p450, CYP 3A4, certain drugs metabolized by that system could accumulate. Although clinically significant interactions of ranolazine with these agents has not been demonstrated, patients on maximum doses of simvastatin, or patients on verapamil or diltiazem will be excluded.
  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: NCT00998218

Locations
United States, Wisconsin
Aspirus Wausau Hospital
Wausau, Wisconsin, United States, 54401
Sponsors and Collaborators
Aspirus Heart and Vascular Institute-Research and Education
Investigators
Principal Investigator: David K. Murdock, MD Aspirus Heart and Vascular Institute-Research and Education
  More Information

Publications:
Responsible Party: Karen Olson, Research Manager, Aspirus Heart and Vascular Institute-Research and Education
ClinicalTrials.gov Identifier: NCT00998218     History of Changes
Other Study ID Numbers: RAN-Twave alt
Study First Received: October 16, 2009
Last Updated: February 8, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Aspirus Heart and Vascular Institute-Research and Education:
Sudden Cardiac Death
Arrythmias
Triggered activity
left ventricular dysfunction

Additional relevant MeSH terms:
Arrhythmias, Cardiac
Death
Death, Sudden, Cardiac
Ventricular Dysfunction, Left
Ventricular Dysfunction
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Heart Arrest
Death, Sudden
Ranolazine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 20, 2014