Efficacy of Ranolazine in Patients With Chronic Total Occlusions of Coronary Arteries

Coronary Artery Disease Clinical Trial

Official title:

The Effectiveness of Ranolazine in Reducing Cardiac Ischaemia Induced by Chronic Total Occlusions of Coronary Arteries

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02423265
• Other study ID #: IN-US-259-0172 Buch ISR
• Secondary ID: UMCIRB 13-001574
• Status: Withdrawn
• Phase: Phase 4
• Start date: June 2015
• Est. completion date: March 2017

Study information

• Verified date: March 2023
• Source: East Carolina University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: March 2017
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Angina, Stable
• Arteriosclerosis
• Chronic Stable Angina
• Coronary Artery Disease
• Ischemia
• Myocardial Ischemia

Intervention

Drug:
• Ranolazine
Ranolazine: 500 mg twice day, up-titrated after 1 week to 1000 mg twice a day
• Placebo
Matching placebo: up-titration after 1 week

Locations

Country	Name	City	State
United States	East Carolina Heart Institute at Vidant Medical Center	Greenville	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
East Carolina University	Gilead Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cardiac MRI (CMR) strain	The extent of reversibly ischaemic LV myocardium will be assessed using CMR strain at rest and stress	8 weeks
Secondary	Dobutamine wall motion scoring index (WMSI)	CMR derived end point	8 weeks
Secondary	Quality of Life/burden of angina	QoL questionnaire based assessment (Seattle Angina Quesstionnaire, SAQ; Duke Activity Status Index, DASI;Medical Outcomes Study-Short Form12 )	8 weeks
Secondary	Treadmill ECG exercise distance	Functional capacity assessment	8 weeks
Secondary	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	8 weeks