Atherosclerotic Coronary Vascular Disease
Conditions
Keywords
Cardiovascular disease, Exercise Treadmill Test, Ranolazine, Angina, Myocardial ischemia
Brief summary
The study was designed to evaluate the use of ETT electrocardiogram (ECG) indices as biomarkers in the assessment of atherosclerotic coronary vascular disease (ASCVD).
Interventions
Ranolazine 500 mg, oral tablet, b.i.d.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* History of stable coronary artery disease
Exclusion criteria
* Inability or unwillingness to participate in multiple exercise treadmill tests and/or any other requirements of this study as assessed by the Investigator. * History of chronic atrial fibrillation. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Maximum ST Segment Change Adjusted for Heart Rate (ST-HR) Index | Baseline up to Day 15 | ST/HR index was measured as the average change in ST segment depression relative to heart rate change over the entire duration of exercise, monitored by ECG during the exercise treadmill tests. Change in maximum ST/HR index between the average of tests 1-3 (pre Ranexa® treatment) performed during baseline period and test 4 (post Ranexa® treatment) during treatment period was reported. |
| Change From Baseline in Maximum ST Segment Change Adjusted for Heart Rate (ST-HR) Slope | Baseline up to Day 15 | ST-HR slope is an index of exercise induced ischemia. Linear regression was used to determine the slope of the ST/HR relationship in a participant's ECG response monitored during the exercise treadmill test. The highest ST segment/heart rate slope from among all the ECG leads and the X-axis intercept of the associated line were used to generate the maximum slope. Change in maximum ST-HR slope between the average of tests 1-3 (pre Ranexa® treatment) performed during baseline period and test 4 (post Ranexa® treatment) during treatment period was reported. |
| Change From Baseline in X-Axis Intercept of ST-HR Slope | Baseline up to Day 15 | Linear regression was used to determine the slope of the ST/HR relationship in a participant's ECG response monitored during the exercise treadmill test. Change in X- axis intercept of ST-HR slope between the average of tests 1-3 (pre Ranexa® treatment) performed during baseline period and test 4 (post Ranexa® treatment) during treatment period was reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Total Exercise Duration | Baseline up to Day 15 | Total exercise duration was defined as the elapsed time between the start of exercise and termination of exercise for severe angina, dyspnea or extreme fatigue assessed during the exercise treadmill test. Change in the duration of exercise between the average of tests 1-3 (pre Ranexa® treatment) performed during baseline period and test 4 (post Ranexa® treatment) during treatment period was reported. |
| Change From Baseline in Time to Onset of 1 mm ST Segment Depression (Time to Ischemia) | Baseline up to Day 15 | Exercise-induced ischemia was defined as the new development of horizontal or down sloping ST-segment depression (≥ 1 mm at 60 milliseconds after the J point) vs. baseline tracings. Change in time to onset of 1 mm ST depression between the average of tests 1-3 (pre Ranexa® treatment) performed during baseline period and test 4 (post Ranexa® treatment) during treatment period was reported. |
| Change From Baseline in Time to Onset of Angina | Baseline up to Day 15 | Time to onset of angina was defined as the elapsed time between the start of exercise and the onset of anginal chest pain as reported by the participant. Change in time to angina between the average of tests 1-3 (pre Ranexa® treatment) performed during baseline period and test 4 (post Ranexa® treatment) during treatment period was reported. |
Countries
United States
Participant flow
Recruitment details
A total of 14 participants took part in the study from 9 March 2012 to 2 January 2014.
Pre-assignment details
All enrolled participants (N=14) with evidence of exercise induced ischemia \[≥ 1 millimeter (mm) ST depression\] on the ECG monitoring during exercise treadmill test 1 (ETT 1) and who achieved ≤ 20% variation in exercise duration between consecutive ETTs during baseline period were included in the treatment period. One participant did not provide interpretable treadmill data and was not included in the analysis of primary and secondary variables.
Participants by arm
| Arm | Count |
|---|---|
| Ranolazine 500 mg Participants received ranolazine, 500 mg, orally, b.i.d., up to 14 days. | 14 |
| Total | 14 |
Baseline characteristics
| Characteristic | Ranolazine 500 mg |
|---|---|
| Age, Continuous | 64.0 years STANDARD_DEVIATION 7.75 |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 14 |
| other Total, other adverse events | 3 / 14 |
| serious Total, serious adverse events | 0 / 14 |
Outcome results
Primary
Change From Baseline in Maximum ST Segment Change Adjusted for Heart Rate (ST-HR) Index
ST/HR index was measured as the average change in ST segment depression relative to heart rate change over the entire duration of exercise, monitored by ECG during the exercise treadmill tests. Change in maximum ST/HR index between the average of tests 1-3 (pre Ranexa® treatment) performed during baseline period and test 4 (post Ranexa® treatment) during treatment period was reported.
Time frame: Baseline up to Day 15
Population: Safety Analysis Set included all enrolled participants who met the inclusion/exclusion criteria and had at least one post-baseline assessment. Number analyzed were the number of participants with data available for analysis at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ranolazine 500 mg | Change From Baseline in Maximum ST Segment Change Adjusted for Heart Rate (ST-HR) Index | Test 1 | 3.211 microvolts/beats per minute (microV/bpm) | Standard Deviation 1.6553 |
| Ranolazine 500 mg | Change From Baseline in Maximum ST Segment Change Adjusted for Heart Rate (ST-HR) Index | Test 2 | 2.822 microvolts/beats per minute (microV/bpm) | Standard Deviation 1.0289 |
| Ranolazine 500 mg | Change From Baseline in Maximum ST Segment Change Adjusted for Heart Rate (ST-HR) Index | Test 3 | 3.228 microvolts/beats per minute (microV/bpm) | Standard Deviation 1.891 |
| Ranolazine 500 mg | Change From Baseline in Maximum ST Segment Change Adjusted for Heart Rate (ST-HR) Index | Test 4 | 2.502 microvolts/beats per minute (microV/bpm) | Standard Deviation 1.8884 |
| Ranolazine 500 mg | Change From Baseline in Maximum ST Segment Change Adjusted for Heart Rate (ST-HR) Index | Change From Baseline in Maximum ST/Heart Rate Index | -0.605 microvolts/beats per minute (microV/bpm) | Standard Deviation 1.0482 |
Primary
Change From Baseline in Maximum ST Segment Change Adjusted for Heart Rate (ST-HR) Slope
ST-HR slope is an index of exercise induced ischemia. Linear regression was used to determine the slope of the ST/HR relationship in a participant's ECG response monitored during the exercise treadmill test. The highest ST segment/heart rate slope from among all the ECG leads and the X-axis intercept of the associated line were used to generate the maximum slope. Change in maximum ST-HR slope between the average of tests 1-3 (pre Ranexa® treatment) performed during baseline period and test 4 (post Ranexa® treatment) during treatment period was reported.
Time frame: Baseline up to Day 15
Population: Safety Analysis Set included all enrolled participants who met the inclusion/exclusion criteria and had at least one post-baseline assessment. Number analyzed were the number of participants with data available for analysis at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ranolazine 500 mg | Change From Baseline in Maximum ST Segment Change Adjusted for Heart Rate (ST-HR) Slope | Test 1 | 4.857 microvolts/beat/minute (microV/beat/min) | Standard Deviation 2.3042 |
| Ranolazine 500 mg | Change From Baseline in Maximum ST Segment Change Adjusted for Heart Rate (ST-HR) Slope | Test 2 | 5.318 microvolts/beat/minute (microV/beat/min) | Standard Deviation 3.0996 |
| Ranolazine 500 mg | Change From Baseline in Maximum ST Segment Change Adjusted for Heart Rate (ST-HR) Slope | Test 3 | 4.645 microvolts/beat/minute (microV/beat/min) | Standard Deviation 2.2869 |
| Ranolazine 500 mg | Change From Baseline in Maximum ST Segment Change Adjusted for Heart Rate (ST-HR) Slope | Test 4 | 3.430 microvolts/beat/minute (microV/beat/min) | Standard Deviation 2.7374 |
| Ranolazine 500 mg | Change From Baseline in Maximum ST Segment Change Adjusted for Heart Rate (ST-HR) Slope | Change From Baseline in Maximum ST/Heart Rate Slope | -1.553 microvolts/beat/minute (microV/beat/min) | Standard Deviation 3.12 |
Primary
Change From Baseline in X-Axis Intercept of ST-HR Slope
Linear regression was used to determine the slope of the ST/HR relationship in a participant's ECG response monitored during the exercise treadmill test. Change in X- axis intercept of ST-HR slope between the average of tests 1-3 (pre Ranexa® treatment) performed during baseline period and test 4 (post Ranexa® treatment) during treatment period was reported.
Time frame: Baseline up to Day 15
Population: Safety Analysis Set included all enrolled participants who met the inclusion/exclusion criteria and had at least one post-baseline assessment. Number analyzed were the number of participants with data available for analysis at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ranolazine 500 mg | Change From Baseline in X-Axis Intercept of ST-HR Slope | Test 1 | 93.4 beats per minute (bpm) | Standard Deviation 21.33 |
| Ranolazine 500 mg | Change From Baseline in X-Axis Intercept of ST-HR Slope | Test 2 | 88.1 beats per minute (bpm) | Standard Deviation 27.3 |
| Ranolazine 500 mg | Change From Baseline in X-Axis Intercept of ST-HR Slope | Test 3 | 89.8 beats per minute (bpm) | Standard Deviation 19.39 |
| Ranolazine 500 mg | Change From Baseline in X-Axis Intercept of ST-HR Slope | Test 4 | 89.2 beats per minute (bpm) | Standard Deviation 24.34 |
| Ranolazine 500 mg | Change From Baseline in X-Axis Intercept of ST-HR Slope | Change From Baseline in X-axis Intercept of ST/Heart Rate Slope | 2.173 beats per minute (bpm) | Standard Deviation 8.7326 |
Secondary
Change From Baseline in Time to Onset of 1 mm ST Segment Depression (Time to Ischemia)
Exercise-induced ischemia was defined as the new development of horizontal or down sloping ST-segment depression (≥ 1 mm at 60 milliseconds after the J point) vs. baseline tracings. Change in time to onset of 1 mm ST depression between the average of tests 1-3 (pre Ranexa® treatment) performed during baseline period and test 4 (post Ranexa® treatment) during treatment period was reported.
Time frame: Baseline up to Day 15
Population: Safety Analysis Set included all enrolled participants who met the inclusion/exclusion criteria and had at least one post-baseline assessment. Number analyzed were the number of participants with data available for analysis at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ranolazine 500 mg | Change From Baseline in Time to Onset of 1 mm ST Segment Depression (Time to Ischemia) | Test 4 | 9.343 minutes | Standard Deviation 4.1114 |
| Ranolazine 500 mg | Change From Baseline in Time to Onset of 1 mm ST Segment Depression (Time to Ischemia) | Test 1 | 8.611 minutes | Standard Deviation 3.8054 |
| Ranolazine 500 mg | Change From Baseline in Time to Onset of 1 mm ST Segment Depression (Time to Ischemia) | Test 2 | 8.833 minutes | Standard Deviation 3.2241 |
| Ranolazine 500 mg | Change From Baseline in Time to Onset of 1 mm ST Segment Depression (Time to Ischemia) | Test 3 | 9.196 minutes | Standard Deviation 3.6141 |
| Ranolazine 500 mg | Change From Baseline in Time to Onset of 1 mm ST Segment Depression (Time to Ischemia) | Change From Baseline in Time to Onset of 1 mm ST Depression | 0.876 minutes | Standard Deviation 1.0227 |
Secondary
Change From Baseline in Time to Onset of Angina
Time to onset of angina was defined as the elapsed time between the start of exercise and the onset of anginal chest pain as reported by the participant. Change in time to angina between the average of tests 1-3 (pre Ranexa® treatment) performed during baseline period and test 4 (post Ranexa® treatment) during treatment period was reported.
Time frame: Baseline up to Day 15
Population: Safety Analysis Set included all enrolled participants who met the inclusion/exclusion criteria and had at least one post-baseline assessment. Number analyzed were the number of participants with data available for analysis at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ranolazine 500 mg | Change From Baseline in Time to Onset of Angina | Test 1 | 8.693 minutes | Standard Deviation 2.4635 |
| Ranolazine 500 mg | Change From Baseline in Time to Onset of Angina | Test 2 | 7.575 minutes | Standard Deviation 1.9806 |
| Ranolazine 500 mg | Change From Baseline in Time to Onset of Angina | Test 3 | 8.189 minutes | Standard Deviation 1.5457 |
| Ranolazine 500 mg | Change From Baseline in Time to Onset of Angina | Test 4 | 8.037 minutes | Standard Deviation 3.6395 |
| Ranolazine 500 mg | Change From Baseline in Time to Onset of Angina | Change From Baseline in Time to Onset of Angina | 0.473 minutes | Standard Deviation 3.3342 |
Secondary
Change From Baseline in Total Exercise Duration
Total exercise duration was defined as the elapsed time between the start of exercise and termination of exercise for severe angina, dyspnea or extreme fatigue assessed during the exercise treadmill test. Change in the duration of exercise between the average of tests 1-3 (pre Ranexa® treatment) performed during baseline period and test 4 (post Ranexa® treatment) during treatment period was reported.
Time frame: Baseline up to Day 15
Population: Safety Analysis Set included all enrolled participants who met the inclusion/exclusion criteria and had at least one post-baseline assessment. Number analyzed were the number of participants with data available for analysis at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ranolazine 500 mg | Change From Baseline in Total Exercise Duration | Test 1 | 11.118 minutes | Standard Deviation 3.3519 |
| Ranolazine 500 mg | Change From Baseline in Total Exercise Duration | Test 2 | 11.008 minutes | Standard Deviation 3.3765 |
| Ranolazine 500 mg | Change From Baseline in Total Exercise Duration | Test 3 | 11.150 minutes | Standard Deviation 3.4652 |
| Ranolazine 500 mg | Change From Baseline in Total Exercise Duration | Test 4 | 11.892 minutes | Standard Deviation 3.7094 |
| Ranolazine 500 mg | Change From Baseline in Total Exercise Duration | Change From Baseline in Total Exercise Duration | 0.755 minutes | Standard Deviation 0.9834 |