Efficacy of Ranolazine in Patients With Chronic Total Occlusions of Coronary Arteries
| Status: | Withdrawn |
|---|---|
| Conditions: | Angina, Peripheral Vascular Disease, Peripheral Vascular Disease, Cardiology |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 21 - Any |
| Updated: | 6/1/2018 |
| Start Date: | June 2015 |
| End Date: | March 2017 |
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.
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.
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.
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.
Inclusion Criteria:
- 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
- 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
We found this trial at
1
site
526 Moye Boulevard
Greenville, North Carolina 27834
Greenville, North Carolina 27834
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