Angina
Conditions
Keywords
deferred percutaneous coronary intervention, fractional flow reserve
Brief summary
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
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
Interventions
DRUGSugar pill
1. 500mg tablet two times per day for 7 days then, 2. 500mg tablet (1000mg) two times per day for 15 weeks
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
Sponsors
Gilead Sciences
North Florida Foundation for Research and Education
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Seattle Angina Questionnaire Score Change From Baseline to 16 Weeks | Change in 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). . |
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 | Number of participants who reported adverse events for ischemia driven revascularization or hospitalization |
Countries
United States
Participant flow
Recruitment details
recruitment period first subject enrolled 9/24/2014 to last subject enrolled 12/12/2015
Participants by arm
| Arm | Count |
|---|---|
| Ranolazine Ranolazine 500 mg tablets
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 | 25 |
| 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: 1. 500mg tablet two times per day for 7 days then, 2. 500mg tablet (1000mg) two times per day for 15 weeks | 25 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
| Overall Study | started on excluded medication | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Ranolazine | Sugar Pill | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 15 Participants | 13 Participants | 28 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 12 Participants | 22 Participants |
| Diabetes mellitus | 14 Participants | 16 Participants | 30 Participants |
| history of Coronary Artery Bypass Graft surgery | 8 Participants | 6 Participants | 14 Participants |
| history of Percutaneous Coronary Intervention | 19 Participants | 14 Participants | 33 Participants |
| Hyperlipidemia | 16 Participants | 17 Participants | 33 Participants |
| Hypertension | 25 Participants | 25 Participants | 50 Participants |
| on Insulin | 5 Participants | 7 Participants | 12 Participants |
| Region of Enrollment United States | 25 participants | 25 participants | 50 participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 24 Participants | 25 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 25 | 0 / 25 |
| other Total, other adverse events | 17 / 25 | 15 / 25 |
| serious Total, serious adverse events | 5 / 25 | 4 / 25 |
Outcome results
Primary
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). .
Time frame: Change in baseline to 16 weeks
Population: by intention to treat, 46 subjects had baseline and follow up SAQ data completed at 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ranolazine | Seattle Angina Questionnaire Score Change From Baseline to 16 Weeks | Angina Stablility 16 weeks | 58 units on a scale | Standard Deviation 26 |
| Ranolazine | Seattle Angina Questionnaire Score Change From Baseline to 16 Weeks | Angina Frequency group difference | 16 units on a scale | Standard Deviation 36 |
| Ranolazine | Seattle Angina Questionnaire Score Change From Baseline to 16 Weeks | Physical Limitation 16 weeks | 40 units on a scale | Standard Deviation 19 |
| Ranolazine | Seattle Angina Questionnaire Score Change From Baseline to 16 Weeks | Treatment Satisfaction baseline | 80 units on a scale | Standard Deviation 19 |
| Ranolazine | Seattle Angina Questionnaire Score Change From Baseline to 16 Weeks | Angia Stability group difference | 19 units on a scale | Standard Deviation 36 |
| Ranolazine | Seattle Angina Questionnaire Score Change From Baseline to 16 Weeks | Treatment Statisfaction 16 weeks | 77 units on a scale | Standard Deviation 26 |
| Ranolazine | Seattle Angina Questionnaire Score Change From Baseline to 16 Weeks | Angina Stability baseline | 39 units on a scale | Standard Deviation 28 |
| Ranolazine | Seattle Angina Questionnaire Score Change From Baseline to 16 Weeks | Treatment Satisfaciton group difference | -4 units on a scale | Standard Deviation 26 |
| Ranolazine | Seattle Angina Questionnaire Score Change From Baseline to 16 Weeks | Angina Frequency baseline | 65 units on a scale | Standard Deviation 24 |
| Ranolazine | Seattle Angina Questionnaire Score Change From Baseline to 16 Weeks | Quality of Life baseline | 37 units on a scale | Standard Deviation 24 |
| Ranolazine | Seattle Angina Questionnaire Score Change From Baseline to 16 Weeks | Physical Limitation group difference | -7 units on a scale | Standard Deviation 27 |
| Ranolazine | Seattle Angina Questionnaire Score Change From Baseline to 16 Weeks | Quality of Life 16 weeks | 56 units on a scale | Standard Deviation 29 |
| Ranolazine | Seattle Angina Questionnaire Score Change From Baseline to 16 Weeks | Angina Frequency 16 weeks | 81 units on a scale | Standard Deviation 23 |
| Ranolazine | Seattle Angina Questionnaire Score Change From Baseline to 16 Weeks | Quality of Life group difference | 21 units on a scale | Standard Deviation 32 |
| Ranolazine | Seattle Angina Questionnaire Score Change From Baseline to 16 Weeks | Physical Limitation baseline | 48 units on a scale | Standard Deviation 25 |
| Sugar Pill | Seattle Angina Questionnaire Score Change From Baseline to 16 Weeks | Quality of Life group difference | 18 units on a scale | Standard Deviation 31 |
| Sugar Pill | Seattle Angina Questionnaire Score Change From Baseline to 16 Weeks | Physical Limitation baseline | 50 units on a scale | Standard Deviation 20 |
| Sugar Pill | Seattle Angina Questionnaire Score Change From Baseline to 16 Weeks | Physical Limitation 16 weeks | 60 units on a scale | Standard Deviation 24 |
| Sugar Pill | Seattle Angina Questionnaire Score Change From Baseline to 16 Weeks | Physical Limitation group difference | 6 units on a scale | Standard Deviation 20 |
| Sugar Pill | Seattle Angina Questionnaire Score Change From Baseline to 16 Weeks | Angina Stability baseline | 37 units on a scale | Standard Deviation 28 |
| Sugar Pill | Seattle Angina Questionnaire Score Change From Baseline to 16 Weeks | Angina Stablility 16 weeks | 55 units on a scale | Standard Deviation 27 |
| Sugar Pill | Seattle Angina Questionnaire Score Change From Baseline to 16 Weeks | Angia Stability group difference | 18 units on a scale | Standard Deviation 32 |
| Sugar Pill | Seattle Angina Questionnaire Score Change From Baseline to 16 Weeks | Angina Frequency baseline | 64 units on a scale | Standard Deviation 23 |
| Sugar Pill | Seattle Angina Questionnaire Score Change From Baseline to 16 Weeks | Angina Frequency 16 weeks | 80 units on a scale | Standard Deviation 24 |
| Sugar Pill | Seattle Angina Questionnaire Score Change From Baseline to 16 Weeks | Angina Frequency group difference | 15 units on a scale | Standard Deviation 27 |
| Sugar Pill | Seattle Angina Questionnaire Score Change From Baseline to 16 Weeks | Treatment Satisfaction baseline | 85 units on a scale | Standard Deviation 18 |
| Sugar Pill | Seattle Angina Questionnaire Score Change From Baseline to 16 Weeks | Treatment Statisfaction 16 weeks | 82 units on a scale | Standard Deviation 22 |
| Sugar Pill | Seattle Angina Questionnaire Score Change From Baseline to 16 Weeks | Treatment Satisfaciton group difference | -3 units on a scale | Standard Deviation 26 |
| Sugar Pill | Seattle Angina Questionnaire Score Change From Baseline to 16 Weeks | Quality of Life baseline | 45 units on a scale | Standard Deviation 27 |
| Sugar Pill | Seattle Angina Questionnaire Score Change From Baseline to 16 Weeks | Quality of Life 16 weeks | 63 units on a scale | Standard Deviation 18 |
Comparison: between group comparison for all SAQ domainsp-value: >0.05t-test, 2 sided
Comparison: within group comparison of change from baselinep-value: >0.05paired t test
Comparison: within group comparison of change from baselinep-value: <0.05paired t test
Comparison: within group comparison of change from baselinep-value: >0.05paired t test
Comparison: within group comparison of change from baselinep-value: <0.05paired t test
Secondary
Ischemia Driven Revascularization or Hospitalization
Number of participants who reported adverse events for ischemia driven revascularization or hospitalization
Time frame: 4 month
Population: the incidence of ischemia driven hospitalization or catheterization was assessed for all subjects.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ranolazine | Ischemia Driven Revascularization or Hospitalization | 3 Participants |
| Sugar Pill | Ischemia Driven Revascularization or Hospitalization | 5 Participants |
p-value: >0.05Fisher Exact
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
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Ranolazine | Subjective Well Being | Baseline | excellent/good | 9 Participants |
| Ranolazine | Subjective Well Being | Baseline | fair/poor | 12 Participants |
| Ranolazine | Subjective Well Being | Baseline | missing | 1 Participants |
| Ranolazine | Subjective Well Being | 16 Weeks | excellent/good | 11 Participants |
| Ranolazine | Subjective Well Being | 16 Weeks | fair/poor | 10 Participants |
| Ranolazine | Subjective Well Being | 16 Weeks | missing | 1 Participants |
| Sugar Pill | Subjective Well Being | 16 Weeks | fair/poor | 10 Participants |
| Sugar Pill | Subjective Well Being | Baseline | excellent/good | 6 Participants |
| Sugar Pill | Subjective Well Being | 16 Weeks | excellent/good | 10 Participants |
| Sugar Pill | Subjective Well Being | Baseline | fair/poor | 16 Participants |
| Sugar Pill | Subjective Well Being | 16 Weeks | missing | 4 Participants |
| Sugar Pill | Subjective Well Being | Baseline | missing | 2 Participants |
Comparison: between group comparison for the excellent/goodp-value: 0.58Fisher Exact
Comparison: Between group analysis for fair/poorp-value: 0.8Fisher Exact
Comparison: within group analysis of change from baseline for excellent/goodp-value: 0.5McNemar
Comparison: within group comparison of change from baseline for fair/poorp-value: 0.48McNemar
Comparison: within group analysis of change from baseline for excellent/goodp-value: 0.19McNemar
Comparison: within group comparison of change from baseline for fair/poorp-value: 0.067McNemar