Microvascular Assessment of Ranolazine in Non-Obstructive Atherosclerosis (MARINA)

NCT ID: NCT02147067

Last Updated: 2019-05-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-30
• Study Completion Date: 2018-06-30

Brief Summary

The purpose of this study is to look at the effects of the drug Ranolazine compared to Placebo on symptoms of chest pain or chest tightness (known as angina), exercise endurance and ability, and changes in blood flow to the very small arteries of the heart (known as coronary microvascular function) in patients who do not have significant blockages in their major heart arteries. Ranolazine is a drug that is already approved by the FDA for angina, but it may be particularly effective in people with disease in their tiny heart vessels (known as coronary microvascular disease).

This trial aims to enroll 50 patients with angina who undergo baseline bicycle exercise testing with monitoring of the heart's electrical activity and oxygen consumption (known as cardiopulmonary exercise test) and coronary angiogram (taking pictures of the heart arteries through small hollow tubes placed through the wrist or groin). If severe blockages in the main arteries are not found then testing for coronary microvascular function will be performed. Subsequently, participants will then be randomized 50/50 to either Ranolazine or Placebo. After taking the study drug for 12 weeks, they will then repeat the cardiopulmonary exercise test and the coronary angiogram with testing for microvascular function.

Detailed Description

Heart disease is the most common cause of death in the world. Most of our understanding of heart disease has involved the large heart arteries (epicardial arteries); however, disease of the very small heart arteries (coronary microvasculature) likely precedes the development of epicardial disease and represents the "base of the iceberg" of cardiovascular disease. Yet, we do not understand how dysfunctional microvasculature leads to reduced blood flow, symptoms and adverse outcomes.

Coronary microvascular disease results from a combination of structural and functional abnormalities, so it is important to have reliable diagnostic tools that do not rely solely on imaging. The gold-standard for testing involves hemodynamic (blood circulation) measurements such as coronary flow reserve (CFR) and hyperemic microcirculatory resistance (HMR) that take place in the cardiac catheterization laboratory.

Ranolazine is a relatively new U.S Food and Drug Administration-approved medicine to help with angina (chest pain). There are no publications on the effect of Ranolazine on HMR.

Conditions

Microvascular Angina

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Ranolazine

Ranolazine 1,000 mg twice daily

Group Type: EXPERIMENTAL

Ranolazine

Intervention Type: DRUG

Ranolazine 1,000 mg twice daily

Placebo

Placebo twice daily

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Interventions

Ranolazine

Ranolazine 1,000 mg twice daily

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Other Intervention Names

Ranexa

Eligibility Criteria

Inclusion Criteria

• History of typical angina or effort-induced anginal symptoms and are currently experiencing angina at least once per week
• Abnormal stress ECG, exercise stress imaging, or pharmacological stress imaging
• Non-obstructive coronary artery disease as defined by lesion stenosis ≤ 50% in any artery as visualized by diagnostic angiography

Exclusion Criteria

• Inability to provide informed consent
• Active Myocardial Infarction
• History of coronary artery bypass grafting
• Diagnosis of other specific cardiac disease such as severe valvular heart disease, cardiomyopathy, or variant angina
• Left Ventricular Ejection Fraction (LVEF) < 30%
• Known renal insufficiency (CrCl < 30 mL/min) or on dialysis
• Contraindications to the use of Ranolazine

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Habib Samady

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Habib Samady, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Emory University

Atlanta, Georgia, United States

Countries

United States

References

Koh JS, Hung OY, Eshtehardi P, Kumar A, Rabah R, Raad M, Kumar S, Chaudhry S, Gupta S, Hosseini H, Brilakis E, Corban M, Sabbak N, Burnett GM, Liu C, Mehta PK, Quyyumi AA, Samady H. Microvascular Assessment of Ranolazine in Non-Obstructive Atherosclerosis: The MARINA Randomized, Double-Blinded, Controlled Pilot Trial. Circ Cardiovasc Interv. 2020 Dec;13(12):e008204. doi: 10.1161/CIRCINTERVENTIONS.119.008204. Epub 2020 Dec 4.

Reference Type: DERIVED

PMID: 33272036 (View on PubMed)

Titterington JS, Hung OY, Wenger NK. Microvascular angina: an update on diagnosis and treatment. Future Cardiol. 2015 Mar;11(2):229-42. doi: 10.2217/fca.14.79.

Reference Type: DERIVED

PMID: 25760881 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IRB00072996

Identifier Type: -

Identifier Source: org_study_id