Ranolazine Among Unrevascularized Chronic Stable Angina Patients

Study Overview
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Brief Summary
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This is a prospective, double-blind, placebo-controlled, randomized, single-center (North Florida- South Georgia VA Medical Center) study. The study objective is to determine if ranolazine improves angina symptoms at 4 months compared with placebo among stable coronary artery disease patients who have demonstrable myocardial ischemia, but who do not undergo revascularization

Detailed Description
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This is a prospective, double-blind, placebo-controlled, randomized, single-center (North Florida- South Georgia VA Medical Center) study. The study objective is to determine if ranolazine improves angina symptoms at 4 months compared with placebo among stable coronary artery disease patients who have demonstrable myocardial ischemia, but who do not undergo revascularization. Baseline Procedure: Assessments performed exclusively to determine eligibility for this study would be done only after obtaining informed consent. Assessments performed for clinical indications (not exclusively to determine study eligibility) may be used for baseline values even if the studies were done before informed consent was obtained. The assessment will include: Informed Consent Review subject eligibility criteria FFR value calculated at the time of cardiac catheterization Review previous and concomitant medications Frequency of symptoms and quality of life prior to study according to Seattle Angina Questionnaire (SAQ) Screening Visit: The assessments to determine eligibility are: Review of eligibility criteria Review of cardiac catheterization and FFR Review of medications taken in the past 30 days Subjects that meet eligibility criteria will be randomized to receive either the active drug, Ranolazine or a matching placebo (non-active drug). Staff and subjects will not know if the subject will be receiving the active drug or the placebo. Drug schedule will be as follows: 1st dose of one tablet (500mg) will begin the evening of Day 1 On Days 2-7, one tablet (500mg) two times a day (12-hours apart). On Day 8, increase dose of study drug to two tablets (1000mg) twice a day; once in the morning and once in the evening, 12 hours apart. This dose will continue for the duration of the study. The study drug can be taken with or without food. Telephone Follow-up: One week phone calls will be made to determine well being, adverse events, answer questions and remind subjects to increase the study medication dose. Month 4 Follow-up: Frequency of symptoms and quality of life according to Seattle Angina Questionnaire (SAQ) Assessment of well-being Any hospitalizations or the need for revascularization

Official Title
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Improvement of Subjective Well-Being by Ranolazine Among Unrevascularized Chronic Stable Coronary Artery Disease Patients

Conditions
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Angina

Intervention / Treatment
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* Drug: Ranolazine
* Drug: Sugar pill


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients >= 18 years of age referred for cardiac catheterization for evaluation of cardiac symptoms ( angina, fatigue, or shortness of breath) At least 1 indeterminate stenosis (20-80%), Fractional flow reserve (FFR) <=0.8 and PCI deferred Exclusion Criteria: Coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting) during the index procedure or anticipated within the next month acute coronary syndrome or cardiogenic shock QTc > 500 milliseconds use of strong inhibitors of CTP3A (i.e. ketoconazole, itraconazole, clarithromycin,nefazodone, nelfinavir, ritonavir, indinavir and saquinavir) use of inducers of CYP3A (i.e. rifampin, rifabutin, rifapentine, phenobarbital, phenytoin, carbamazepine, and St. John's wort) liver cirrhosis sever renal insufficiency (i.e. creatinine clearance < 30mL/min/1.73 m2)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ranolazine<br>Ranolazine 500 mg tablets 500mg tablet two times per day for 7 days then, 500mg tablet (1000mg) two times per day for 15 weeks | Drug: Ranolazine<br>* Ranolazine 500mg tablet 500mg tablet two times per day for 7 days then, 500mg tablet (1000mg) two times per day for 15 weeks<br>* Other names: Ranexa;|
| Placebo Comparator: Sugar pill<br>Sugar pill that looks like the drug ranolazine 500mg tablet 500mg tablet two times per day for 7 days then, 500mg tablet (1000mg) two times per day for 15 weeks | Drug: Sugar pill<br>* 500mg tablet two times per day for 7 days then, 500mg tablet (1000mg) two times per day for 15 weeks<br>* Other names: placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seattle Angina Questionnaire Score Change From Baseline to 16 Weeks | The SAQ quantifies patients' physical limitations caused by angina, the frequency of and recent changes in their symptoms, their satisfaction with treatment, and the degree to which they perceive their disease to affect their quality of life.Each of the 5 dimensions are scored by assigning eachresponse an ordinal value, beginning with 1 for the response that implies the lowest level of functioning, and summing across items within each of the 5 scales. Scale scores then transformed to 0-100 range by subtracting the lowest possible scale score, dividing by the range1 / 3 Seattle Angina Questionnaire (SAQ)of the scale and multiplying by 100. No overall scale score is generated. Factors and Each scale is transformed to a score of 0 to 100, where higher scores indicate better function (eg, less physical limitation, less angina, and better quality of life). . | Change in baseline to 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjective Well Being | overall feeling of well being determined from rating of excellent, good, fair or poor at baseline compared to same at month 4 | Compare from baseline to month 4 | 
| Ischemia Driven Revascularization or Hospitalization | Number of participants who reported adverse events for ischemia driven revascularization or hospitalization | 4 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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deferred percutaneous coronary intervention, fractional flow reserve