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

NCT02423265 | Withdrawn Phase 4

• 2 other identifiers: IN-US-259-0172 Buch ISRUMCIRB 13-001574
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Myocardial Ischemia; Coronary Artery Disease; Arteriosclerosis; Chronic Stable Angina

Keywords

Chronic total coronary occlusions; Ranolazine

Outcome Measures

Primary Outcomes (1)

• Cardiac MRI (CMR) strain

  The extent of reversibly ischaemic LV myocardium will be assessed using CMR strain at rest and stress

  8 weeks

Secondary Outcomes (4)

• Dobutamine wall motion scoring index (WMSI)

  8 weeks

• Quality of Life/burden of angina

  8 weeks

• Treadmill ECG exercise distance

  8 weeks

• Time to ECG changes (ST depression) on exercise ECG

  8 weeks

Study Arms (2)

Ranolazine

ACTIVE COMPARATOR

500mg bd ranolazine for 1 week then uptitrated to 1000mg bd to continue for 8 weeks

Drug: Ranolazine

Placebo

PLACEBO COMPARATOR

Matching placebo, with up titration after 1 week as in active treatment arm

Drug: Placebo

Interventions

Ranolazine DRUG

Ranolazine: 500 mg twice day, up-titrated after 1 week to 1000 mg twice a day

Also known as: Renexa

Ranolazine

Placebo DRUG

Matching placebo: up-titration after 1 week

Placebo

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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

Sponsors & Collaborators

• East Carolina University: lead
• Gilead Sciences: collaborator

Study Sites (1)

East Carolina Heart Institute at Vidant Medical Center

Greenville, North Carolina, 27834, United States

Location

MeSH Terms

Conditions

Myocardial Ischemia; Coronary Artery Disease; Arteriosclerosis; Angina, Stable

Interventions

Ranolazine

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Coronary Disease; Arterial Occlusive Diseases; Angina Pectoris; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Ashesh N Buch, MB.ChB, M.D.

  East Carolina University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor Cardiovascular Sciences (Interventional Cardiology)

Study Record Dates

• First Submitted: April 12, 2015
• First Posted: April 22, 2015
• Study Start: June 1, 2015
• Primary Completion: December 1, 2016
• Study Completion: March 1, 2017
• Last Updated: March 13, 2023

Record last verified: 2023-03

Locations

US (1)