Sudden Cardiac DeathPhase 3NCT00998218
Effect of Ranolazine on Arrhythmias and Microvolt T- Wave Alternans (MVTWA) Patients With LV Dysfunction
A Phase 3 study testing Ranolazine in people with Sudden Cardiac Death and Ventricular Arrythmias, run by Aspirus Heart and Vascular Institute-Research and Education at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sudden Cardiac Death, Ventricular Arrythmias
- What is being tested?
- Ranolazine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2009to Dec 2010
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Implant of AICD for the prevention of sudden cardiac death Implant of AICD for the prevention of sudden cardiac death
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Ranolazine on Cardiac Arrhythmias and Microvolt T- Wave Alternans in Patients With Significant Left Ventricular Dysfunction
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.
Read the 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.
- Conditions
- Sudden Cardiac Death, Ventricular Arrythmias
- Being tested
- Ranolazine, Placebo
- Keywords
- Sudden Cardiac Death, Arrythmias, Triggered activity, left ventricular dysfunction
- Medical subject headings
- Death, Sudden, Cardiac, Ventricular Dysfunction, Left
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RanolazineDrug
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
PlaceboDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Ranolazine | Experimental | Ranolazine at 1000 mg BID (or 500 mg BID if the 1000 mg dose was not tolerated) for 4 weeks Receives: Drug: Ranolazine |
| Sugar pill | Placebo comparator | Placebo comparator BID for 4 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: After 4 weeks of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2009 (estimated)
- Study startSep 2009
- Primary completionDec 2010
- Study completionDec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Sudden Cardiac DeathStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aspirus Heart and Vascular Institute-Research and Education
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Karen Olson, Aspirus Heart and Vascular Institute-Research and Education
- Investigators
- David K. Murdock, MD, Principal investigator, Aspirus Heart and Vascular Institute-Research and Education
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00998218
- Sponsor's protocol ID
- RAN-Twave alt
- Status last verified
- Feb 2012
- First submitted
- 16 Oct 2009
- Last updated
- 9 Feb 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Tomaselli 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.
PubMed 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.
PubMed 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.
PubMed 15302796
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Ranolazine on Cardiac Arrhythmias and Microvolt T- Wave Alternans in Patients With Significant Left Ventricular Dysfunction
- ClinicalTrials.gov ID
- NCT00998218
- Acronym / sponsor ID
- RAN-Twave alt
- Conditions
- Sudden Cardiac Death, Ventricular Arrythmias
- Keywords
- Sudden Cardiac Death, Arrythmias, Triggered activity, left ventricular dysfunction
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Aspirus Heart and Vascular Institute-Research and EducationUniversity, hospital or other
- Study start
- Sep 2009
- Primary completion
- Dec 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 20 Oct 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ranolazine | Experimental | Drug: RanolazineRanolazine at 1000 mg BID (or 500 mg BID if the 1000 mg dose was not tolerated) for 4 weeks |
| Sugar pill | Placebo comparator | Drug: PlaceboPlacebo comparator BID for 4 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Implant of AICD for the prevention of sudden cardiac death Implant of AICD for the prevention of sudden cardiac death
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RanolazineRanolazine 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 | Drug | Ranolazine |
| PlaceboRanolazine 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 | Drug | Sugar pill |
Primary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2012.
- Background: PubMed 15486322Tomaselli 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.
- Background: PubMed 16138946Ebinger 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.
- Background: PubMed 15302796Antzelevitch 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David K. Murdock, MD principal investigator
Aspirus Heart and Vascular Institute-Research and Education
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ranolazine in people with Sudden Cardiac Death and Ventricular Arrythmias, run by Aspirus Heart and Vascular Institute-Research and Education at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Feb 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00998218, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2012.