Angina
Conditions
Keywords
deferred percutaneous coronary intervention, fractional flow reserve
Brief summary
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
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.
Interventions
DRUGRanolazine
Ranolazine 500mg tablet 1. 500mg tablet two times per day for 7 days then, 2. 500mg tablet (1000mg) two times per day for 15 weeks
DRUGSugar pill
sugar pill manufactured to mimic ranolazine 500mg tablet 1. 500mg tablet two times per day for 7 days then, 2. 500mg tablet (1000mg) two times per day for 15 weeks
Sponsors
Gilead Sciences
University of Florida
North Florida Foundation for Research and Education
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Seattle Angina Questionnaire Score Change From Baseline to Month 4 | Change in 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Subjective Well Being | Compare from baseline to month 4 | overall feeling of well being determined from rating of excellent, good, fair or poor at baseline compared to same at month 4 |
| Ischemia Driven Revascularization or Hospitalization | 4 month | frequency of the number of reported adverse events for ischemia driven revascularization or hospitalization |
Countries
United States
Participant flow
Recruitment details
5 subjects enrolled. First subjected enrolled 8/7/2015 and last enrolled on 11/19/2015. enrollment discontinued early by investigator due to futility.
Participants by arm
| Arm | Count |
|---|---|
| Ranolazine Ranolazine 500mg tablet
1. 500mg tablet two times per day for 7 days then,
2. 500mg tablet (1000mg) two times per day for 15 weeks
Ranolazine: Ranolazine 500mg tablet
1. 500mg tablet two times per day for 7 days then,
2. 500mg tablet (1000mg) two times per day for 15 weeks | 3 |
| Sugar Pill Sugar pill that looks like the drug ranolazine 500mg tablet
1. 500mg tablet two times per day for 7 days then,
2. 500mg tablet (1000mg) two times per day for 15 weeks
Sugar pill: sugar pill manufactured to mimic ranolazine 500mg tablet
1. 500mg tablet two times per day for 7 days then,
2. 500mg tablet (1000mg) two times per day for 15 weeks | 2 |
| Total | 5 |
Baseline characteristics
| Characteristic | Ranolazine | Sugar Pill | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 2 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 3 | 0 / 2 |
| serious Total, serious adverse events | 0 / 3 | 0 / 2 |
Outcome results
Primary
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).
Time frame: Change in baseline to month 4
Population: The investigator ended this project early due to futility. Do data was analyzed.
Secondary
Ischemia Driven Revascularization or Hospitalization
frequency of the number of reported adverse events for ischemia driven revascularization or hospitalization
Time frame: 4 month
Population: The investigator ended this study early due to futility. No data was analyzed.
Secondary
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
Time frame: Compare from baseline to month 4
Population: The investigator ended this study early due to futility. no data was analyzed.