Ranolazine and Microvascular Angina by PET in the Emergency Department

NCT ID: NCT02052011

Last Updated: 2017-05-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2015-11-30

Brief Summary

The purpose of this study is to determine the effectiveness of Ranolazine for the treatment chest pain from disease of small vessels of the heart also known as 'microvascular angina'.

Detailed Description

The Yale Chest Pain Center (CPC) is a unique clinical lab that provides an integrated interdisciplinary research team, access to high volume of chest pain patients largely free of coronary disease (93%) as well state of the art diagnostics including cardiac PET and a sophisticated system for serum processing and banking facilities. The CPC cohort represents a unique population with unrecognized microvascular disease and is often only accessible through the ED. We propose a one-year pilot study to understand the mechanisms of angina relief by Ranolazine (n=20) in patients with microvessel disease in the ED population as compared to controls (n=10) at baseline and at 1-month. In addition, changes in pain scores and function as measured by Seattle Angina Questionnaire (SAQ), recidivism and costs will be measured and correlated with changes in coronary flow reserve (CFR). Serum samples will be obtained and banked for future marker analysis as intermediate surrogates of outcomes.

Primary aim: To compare changes in coronary flow reserve as measured by cardiac PET in patients receiving Ranolazine versus controls.

Secondary aim: To determine if Ranolazine changes Seattle Angina Questionnaire (SAQ) scores in association with changes in Coronary Flow Reserve (CFR) versus controls.

Exploratory aim: To compare composite rate of return visits (office, emergency department and hospitalization) for chest pain within 4-weeks of enrollment between patients with and without Ranolazine.

Conditions

Microvascular Angina

Study Design

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

Study Groups

Intervention Group

Subjects will take extended release Ranolazine for 4 weeks. Subjects will take 500 mg twice daily for the first week and then 1000 mg twice daily for remaining period (Dosing will be adjusted with concomitant use of diltiazem, verapamil, erythromycin, simvastatin or metformin).

Group Type: EXPERIMENTAL

Ranolazine

Intervention Type: DRUG

Subjects will take the extended-release Ranolazine for a total of 4 weeks. Subjects will take 500 mg twice daily for the first week and then 1000 mg twice daily for remaining period (Dosing will be adjusted with concomitant use of diltiazem, verapamil, erythromycin, simvastatin or metformin).

Placebo Control

Subjects will take placebo pill twice daily for 4 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

Ranolazine

Subjects will take the extended-release Ranolazine for a total of 4 weeks. Subjects will take 500 mg twice daily for the first week and then 1000 mg twice daily for remaining period (Dosing will be adjusted with concomitant use of diltiazem, verapamil, erythromycin, simvastatin or metformin).

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Other Intervention Names

Ranexa

Eligibility Criteria

Inclusion Criteria

• Patients admitted to the Yale ED CPC
• ≥ 30 years age
• chest pain or angina equivalent as their chief complaint within 24 hours of enrollment
• Coronary Flow Reserve(CFR) <2.5 on PET scan in the ED.

Exclusion Criteria

• Acute coronary syndrome
• Prior evidence of obstructive heart disease (history of Percutaneous Transluminal Coronary Angioplasty (PTCA), Coronary Artery Bypass Grafting (CABG) or calcium score > 10 on PET scan)
• Resting blood pressure of systolic >180/110 mm Hg or <100/40
• known cardiomyopathy or heart failure
• currently on dialysis
• creatinine clearance <30 ml/min
• liver cirrhosis
• significant aortic stenosis (murmur on exam)
• active use of cocaine or amphetamine
• current use of potent CYP3A4 inducers or inhibitors (such as ketoconazole, clarithromycin, HIV protease inhibitors)
• baseline QTc > 580 msec
• use of drugs that prolong QTc (Haldol, erythromycin)
• pregnancy
• inability to read or understand English
• suffering from a condition that precludes interview (i.e. cognitive or communication impairment).

• Minimum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Basmah Safdar, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Yale New Haven Hospital

New Haven, Connecticut, United States

Countries

United States

References

Safdar B, D'Onofrio G, Dziura J, Russell RR, Johnson C, Sinusas AJ. Ranolazine and Microvascular Angina by PET in the Emergency Department: Results From a Pilot Randomized Controlled Trial. Clin Ther. 2017 Jan;39(1):55-63. doi: 10.1016/j.clinthera.2016.12.002. Epub 2017 Jan 9.

Reference Type: DERIVED

PMID: 28081848 (View on PubMed)

Other Identifiers

1312013144

Identifier Type: -

Identifier Source: org_study_id