Effectiveness of Ranolazine on Reducing Chest Pain in Patients With Blockage But no Stents

Study Overview
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Brief Summary
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To determine if ranolazine improves angina symptoms at 4 months compared with placebo among patients who are deferred for receiving a Percutaneous Coronary Intervention (PCI) based on the Fractional Flow Reserve (FFR) measurement.

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 patients who are deferred from having a PCI based on the FFR measurement. 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. Two month phone calls will be made to determine well being and adverse events. 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 Subjects will take the study medication for 16 weeks and will receive a phone call from the study coordinator 30 days after last dose of study medication.

Official Title
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Effect of Ranolazine After Deferral of Percutaneous Coronary Intervention by Fractional Flow Reserve (IMWELL3)

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: Stable 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 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 insufficience (i.e. creatinine clearance < 30mL/min/1.73 m2) QTc > 500 milliseconds

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 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 | 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>* sugar pill manufactured to mimic 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: 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 Month 4 | The Seattle Angina Questionnaire is a valid and reliable instrument that measures five clinically important dimensions of health in patients with coronary artery disease (physical limitation, anginal stability, anginal frequency, treatment satisfaction, and disease perception). | Change in baseline to month 4 | 

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 | frequency of the number of 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