ClinicalTrials.gov processed this data on March 29, 2024Link to the current ClinicalTrials.gov record.https://clinicaltrials.gov/ct2/show/NCT00998218RAN-Twave altNCT00998218Effect of Ranolazine on Arrhythmias and Microvolt T- Wave Alternans (MVTWA) Patients With LV DysfunctionThe Effect of Ranolazine on Cardiac Arrhythmias and Microvolt T- Wave Alternans in Patients With Significant Left Ventricular DysfunctionAspirus Heart and Vascular Institute-Research and EducationOtherNo
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.
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.
CompletedSeptember 2009December 2010December 2010Phase 3InterventionalNoRandomizedCrossover AssignmentTreatmentQuadruple (Participant, Care Provider, Investigator, Outcomes Assessor)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 significantAfter 4 weeks of treatment27Sudden Cardiac DeathVentricular ArrythmiasRanolazineExperimentalRanolazine at 1000 mg BID (or 500 mg BID if the 1000 mg dose was not tolerated) for 4 weeksSugar pillPlacebo ComparatorPlacebo comparator BID for 4 weeks.DrugRanolazineRanolazine at 1000 mg BID (or 500 mg BID if the 1000 mg dose was not tolerated) or a comparable placebo for the next 4 weeksRanolazineDrugPlaceboRanolazine at 1000 mg BID (or 500 mg BID if the 1000 mg dose was not tolerated) or a comparable placebo for the next 4 weeksSugar pill
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.
All18 YearsN/ANoDavid K. Murdock, MDPrincipal InvestigatorAspirus Heart and Vascular Institute-Research and EducationAspirus Wausau HospitalWausauWisconsin54401United StatesUnited StatesTomaselli GF, Zipes DP. What causes sudden death in heart failure? Circ Res. 2004 Oct 15;95(8):754-63. doi: 10.1161/01.RES.0000145047.14691.db.15486322Ebinger MW, Krishnan S, Schuger CD. Mechanisms of ventricular arrhythmias in heart failure. Curr Heart Fail Rep. 2005 Sep;2(3):111-7. doi: 10.1007/s11897-005-0018-y.16138946Antzelevitch C, Belardinelli L, Zygmunt AC, Burashnikov A, Di Diego JM, Fish JM, Cordeiro JM, Thomas G. Electrophysiological effects of ranolazine, a novel antianginal agent with antiarrhythmic properties. Circulation. 2004 Aug 24;110(8):904-10. doi: 10.1161/01.CIR.0000139333.83620.5D. Epub 2004 Aug 9.15302796February 2012October 16, 2009October 19, 2009October 20, 2009February 8, 2012February 8, 2012February 9, 2012Principal InvestigatorAspirus Heart and Vascular Institute-Research and EducationKaren OlsonResearch ManagerSudden Cardiac DeathArrythmiasTriggered activityleft ventricular dysfunctionArrhythmias, CardiacVentricular DysfunctionDeath, Sudden, CardiacDeathRanolazine