Trial Outcomes & Findings for Evaluation of Exercise Treadmill Test (ETT) Indices in Participants With Cardiovascular Disease (NCT NCT01562041)

NCT ID: NCT01562041

Last Updated: 2021-06-18

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

14 participants

Primary outcome timeframe

Baseline up to Day 15

Results posted on

2021-06-18

Participant Flow

A total of 14 participants took part in the study from 9 March 2012 to 2 January 2014.

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.

Participant milestones

Participant milestones
Measure
Ranolazine 500 mg
Participants received ranolazine, 500 mg, orally, b.i.d., up to 14 days.
Overall Study
STARTED
14
Overall Study
COMPLETED
14
Overall Study
NOT COMPLETED
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Evaluation of Exercise Treadmill Test (ETT) Indices in Participants With Cardiovascular Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Ranolazine 500 mg
n=14 Participants
Participants received ranolazine, 500 mg, orally, b.i.d., up to 14 days.
Age, Continuous
64.0 years
STANDARD_DEVIATION 7.75 • n=5 Participants
Sex: Female, Male
Female
4 Participants
n=5 Participants
Sex: Female, Male
Male
10 Participants
n=5 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Ranolazine 500 mg
n=13 Participants
Participants received ranolazine, 500 mg, orally, b.i.d., up to 14 days.
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
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
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 1.8910
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
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 outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Ranolazine 500 mg
n=13 Participants
Participants received ranolazine, 500 mg, orally, b.i.d., up to 14 days.
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
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
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
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
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 3.1200

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Ranolazine 500 mg
n=13 Participants
Participants received ranolazine, 500 mg, orally, b.i.d., up to 14 days.
Change From Baseline in X-Axis Intercept of ST-HR Slope
Test 1
93.4 beats per minute (bpm)
Standard Deviation 21.33
Change From Baseline in X-Axis Intercept of ST-HR Slope
Test 2
88.1 beats per minute (bpm)
Standard Deviation 27.30
Change From Baseline in X-Axis Intercept of ST-HR Slope
Test 3
89.8 beats per minute (bpm)
Standard Deviation 19.39
Change From Baseline in X-Axis Intercept of ST-HR Slope
Test 4
89.2 beats per minute (bpm)
Standard Deviation 24.34
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 outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Ranolazine 500 mg
n=13 Participants
Participants received ranolazine, 500 mg, orally, b.i.d., up to 14 days.
Change From Baseline in Total Exercise Duration
Test 1
11.118 minutes
Standard Deviation 3.3519
Change From Baseline in Total Exercise Duration
Test 2
11.008 minutes
Standard Deviation 3.3765
Change From Baseline in Total Exercise Duration
Test 3
11.150 minutes
Standard Deviation 3.4652
Change From Baseline in Total Exercise Duration
Test 4
11.892 minutes
Standard Deviation 3.7094
Change From Baseline in Total Exercise Duration
Change From Baseline in Total Exercise Duration
0.755 minutes
Standard Deviation 0.9834

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Ranolazine 500 mg
n=13 Participants
Participants received ranolazine, 500 mg, orally, b.i.d., up to 14 days.
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
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
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
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
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 outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Ranolazine 500 mg
n=9 Participants
Participants received ranolazine, 500 mg, orally, b.i.d., up to 14 days.
Change From Baseline in Time to Onset of Angina
Test 1
8.693 minutes
Standard Deviation 2.4635
Change From Baseline in Time to Onset of Angina
Test 2
7.575 minutes
Standard Deviation 1.9806
Change From Baseline in Time to Onset of Angina
Test 3
8.189 minutes
Standard Deviation 1.5457
Change From Baseline in Time to Onset of Angina
Test 4
8.037 minutes
Standard Deviation 3.6395
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

Adverse Events

Ranolazine 500 mg

Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Ranolazine 500 mg
n=14 participants at risk
Participants received ranolazine, 500 mg, orally, b.i.d., up to 14 days.
Gastrointestinal disorders
NAUSEA
7.1%
1/14 • From Baseline up to end of study, approximately 21 days.
Safety analysis set included all participants who received at least one dose of the study drug with at least one post-baseline measurement.
Nervous system disorders
DIZZINESS
7.1%
1/14 • From Baseline up to end of study, approximately 21 days.
Safety analysis set included all participants who received at least one dose of the study drug with at least one post-baseline measurement.
Renal and urinary disorders
Haematuria
7.1%
1/14 • From Baseline up to end of study, approximately 21 days.
Safety analysis set included all participants who received at least one dose of the study drug with at least one post-baseline measurement.
Skin and subcutaneous tissue disorders
NIGHT SWEATS
7.1%
1/14 • From Baseline up to end of study, approximately 21 days.
Safety analysis set included all participants who received at least one dose of the study drug with at least one post-baseline measurement.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

  • Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
  • Publication restrictions are in place

Restriction type: OTHER