Myocardial IschemiaPhase 4NCT02423265
Efficacy of Ranolazine in Patients With Chronic Total Occlusions of Coronary Arteries
A Phase 4 study testing Ranolazine in people with Myocardial Ischemia and Coronary Artery Disease, run by East Carolina University at 1 site in United States.
Trial summary
Anti-anginal drugs relieve ischemia and symptoms by reducing myocardial oxygen demand by reducing heart rate and or contractility (beta-blockers, phenylalkylamine and benzothiazepineate classes of calcium antagonists) or vasodilatation of the venous system (fall in pre-load) and coronary vessels. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Myocardial Ischemia, Coronary Artery Disease, Arteriosclerosis
- What is being tested?
- Ranolazine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2015to Mar 2017
- Phase
- Phase 4
- 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 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Angiographically proven coronary artery disease with chronic stable angina for at least 3 months.
- Abnormal stress test (treadmill ECG, nuclear stress test, dobutamine stress echocardiogram or stress perfusion cardiac MRI)
- ≥ 1 chronically occluded coronary artery of a dominant coronary vessel or the left anterior descending artery and/or ≥ 1 occluded vein graft to chronically occluded native coronary vessel
- Subjects must be taking a minimum of 2 anti-anginal agents:
- Exclusion Criteria:• Coronary revascularization in the preceding 2 months
- LVEF < 40
Show all 17Show fewer
- Terminal illness such as cancer
- Occluded recessive coronary vessel
- Hepatic insufficiency,
- Liver cirrhosis,
- Prolonged QT interval on ECG,
- Severe renal failure (see below), Excluding patients with CrCl < 30
- Drugs that are strong inhibitors of CYP3A such as, ketoconazole, macrolide antibiotics and HIV protease inhibitors.
- Limit Ranolazine to 500mg BID in patients on concurrent diltiazem/verapamil
- Limit concurrent simvastatin to 20 mg/day
- Limit concurrent metformin to 1700 mg/day
- Inability to have an MRI scan/known claustrophobia
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
East Carolina Heart Institute at Vidant Medical Center
Greenville, North Carolina, 27834
About this study
Official title: The Effectiveness of Ranolazine in Reducing Cardiac Ischaemia Induced by Chronic Total Occlusions of Coronary Arteries
Anti-anginal drugs relieve ischemia and symptoms by reducing myocardial oxygen demand by reducing heart rate and or contractility (beta-blockers, phenylalkylamine and benzothiazepineate classes of calcium antagonists) or vasodilatation of the venous system (fall in pre-load) and coronary vessels.
Late sodium channels remain open for longer in the presence of myocardial ischaemia. Ranolazine, a novel anti-anginal agent, acts by inhibiting the inward late inward sodium current (INaL), reducing intracellular sodium accumulation and consequently intracellular calcium overload via the sodium/calcium exchanger. It is currently thought that this reduction in intracellular calcium reduces diastolic myocardial stiffness and therefore compression of the small coronary vessels. There is considerable animal data to support this theory.
There are good theoretical reasons to postulate that patients with chronically occluded vessels may derive less benefit from conventional anti-anginal agents, particularly vasodilators. The ischemic myocardium, subtended by the occluded vessel, will already be subject to significant concentrations of paracrine vasodilators such as adenosine. Ranolazine, therefore, may on the basis of its mechanism of action, provide greater relief of ischemia in such patients than conventional anti-anginal agents.
Read the detailed description
To test this hypothesis, a randomized study comparing addition of ranolazine to addition of a minimum of 2 conventional anti-anginal agents in patients with chronic total occlusions would be required. To be sufficiently powered, this would require a significant number of patients recruited in a multi-center trial. This study is an initial pilot study with inactive placebo, not addition of a conventional anti-anginal agent, as the control using MRI imaging data as the primary end-point.
- Being tested
- Ranolazine, Placebo
- Keywords
- Chronic total coronary occlusions, Ranolazine
- Medical subject headings
- Myocardial Ischemia, Coronary Artery Disease, Arteriosclerosis, Angina, Stable
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RanolazineDrug
Also called Renexa
Ranolazine: 500 mg twice day, up-titrated after 1 week to 1000 mg twice a day
PlaceboDrug
Matching placebo: up-titration after 1 week
| Study group | Role | What they receive |
|---|---|---|
| Ranolazine | Active comparator | 500mg bd ranolazine for 1 week then uptitrated to 1000mg bd to continue for 8 weeks Receives: Drug: Ranolazine |
| Placebo | Placebo comparator | Matching placebo, with up titration after 1 week as in active treatment arm Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cardiac MRI (CMR) strain
The extent of reversibly ischaemic LV myocardium will be assessed using CMR strain at rest and stress
Measured: 8 weeks
Secondary outcomes (4)
Dobutamine wall motion scoring index (WMSI)
CMR derived end point
Measured: 8 weeks
Quality of Life/burden of angina
QoL questionnaire based assessment (Seattle Angina Quesstionnaire, SAQ; Duke Activity Status Index, DASI;Medical Outcomes Study-Short Form12 )
Measured: 8 weeks
Treadmill ECG exercise distance
Functional capacity assessment
Measured: 8 weeks
Time to ECG changes (ST depression) on exercise ECG
If baseline ECG permits, this will allow assessment of impact of treatment on ECG markers of ischemia
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2015 (estimated)
- Study startJun 2015
- Primary completionDec 2016 (estimated)
- Study completionMar 2017 (estimated)
Why it stopped: slow recruitment; local new issues with CMR after study start
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myocardial IschemiaStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- East Carolina University
- Sponsor type
- University, hospital or other
- Collaborators
- Gilead Sciences
- Responsible party
- Principal investigator, Dr Ashesh N. Buch, East Carolina University
- Investigators
- Ashesh N Buch, MB.ChB, M.D., Principal investigator, East Carolina University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02423265
- Sponsor's protocol ID
- IN-US-259-0172 Buch ISR
- Other IDs
- UMCIRB 13-001574
- Status last verified
- Mar 2023
- First submitted
- 12 Apr 2015
- Last updated
- 13 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effectiveness of Ranolazine in Reducing Cardiac Ischaemia Induced by Chronic Total Occlusions of Coronary Arteries
- ClinicalTrials.gov ID
- NCT02423265
- Acronym / sponsor ID
- IN-US-259-0172 Buch ISR
- Keywords
- Chronic total coronary occlusions, Ranolazine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: slow recruitment; local new issues with CMR after study start
- Enrolment
- 0 participants (actual)
- Lead sponsor
- East Carolina UniversityUniversity, hospital or other
- Collaborators
- Gilead Sciences
- Study start
- Jun 2015
- Primary completion
- Dec 2016 (estimated)
- Study completion
- Mar 2017 (estimated)
- First posted
- 22 Apr 2015 (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.
Anti-anginal drugs relieve ischemia and symptoms by reducing myocardial oxygen demand by reducing heart rate and or contractility (beta-blockers, phenylalkylamine and benzothiazepineate classes of calcium antagonists) or vasodilatation of the venous system (fall in pre-load) and coronary vessels.
Late sodium channels remain open for longer in the presence of myocardial ischaemia. Ranolazine, a novel anti-anginal agent, acts by inhibiting the inward late inward sodium current (INaL), reducing intracellular sodium accumulation and consequently intracellular calcium overload via the sodium/calcium exchanger. It is currently thought that this reduction in intracellular calcium reduces diastolic myocardial stiffness and therefore compression of the small coronary vessels. There is considerable animal data to support this theory.
There are good theoretical reasons to postulate that patients with chronically occluded vessels may derive less benefit from conventional anti-anginal agents, particularly vasodilators. The ischemic myocardium, subtended by the occluded vessel, will already be subject to significant concentrations of paracrine vasodilators such as adenosine. Ranolazine, therefore, may on the basis of its mechanism of action, provide greater relief of ischemia in such patients than conventional anti-anginal agents.
Detailed description
To test this hypothesis, a randomized study comparing addition of ranolazine to addition of a minimum of 2 conventional anti-anginal agents in patients with chronic total occlusions would be required. To be sufficiently powered, this would require a significant number of patients recruited in a multi-center trial. This study is an initial pilot study with inactive placebo, not addition of a conventional anti-anginal agent, as the control using MRI imaging data as the primary end-point.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ranolazine | Active comparator | Drug: Ranolazine500mg bd ranolazine for 1 week then uptitrated to 1000mg bd to continue for 8 weeks |
| Placebo | Placebo comparator | Drug: PlaceboMatching placebo, with up titration after 1 week as in active treatment arm |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Angiographically proven coronary artery disease with chronic stable angina for at least 3 months.
- Abnormal stress test (treadmill ECG, nuclear stress test, dobutamine stress echocardiogram or stress perfusion cardiac MRI)
- ≥ 1 chronically occluded coronary artery of a dominant coronary vessel or the left anterior descending artery and/or ≥ 1 occluded vein graft to chronically occluded native coronary vessel
- Subjects must be taking a minimum of 2 anti-anginal agents:
- Exclusion Criteria:• Coronary revascularization in the preceding 2 months
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| RanolazineAlso: RenexaRanolazine: 500 mg twice day, up-titrated after 1 week to 1000 mg twice a day | Drug | Ranolazine |
| PlaceboMatching placebo: up-titration after 1 week | Drug | Placebo |
Primary outcome
Cardiac MRI (CMR) strain
Time frame: 8 weeks
The extent of reversibly ischaemic LV myocardium will be assessed using CMR strain at rest and stress
4 secondary outcomes
Dobutamine wall motion scoring index (WMSI)
Time frame: 8 weeks
Quality of Life/burden of angina
Time frame: 8 weeks
Treadmill ECG exercise distance
Time frame: 8 weeks
Time to ECG changes (ST depression) on exercise ECG
Time frame: 8 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2023.
- Individual participant dataSharing planned: Undecided
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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.
Ashesh N Buch, MB.ChB, M.D. principal investigator
East Carolina University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ranolazine in people with Myocardial Ischemia and Coronary Artery Disease, run by East Carolina University 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 17 inclusion and 0 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: withdrawn, as of the sponsor's last update on 13 Mar 2023. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 was withdrawn before enrolling participants, so there are no results.
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?
Cardiac MRI (CMR) strain (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Mar 2023.