Trial Outcomes & Findings for Microvascular Assessment of Ranolazine in Non-Obstructive Atherosclerosis (MARINA) (NCT NCT02147067)
NCT ID: NCT02147067
Last Updated: 2019-05-21
Results Overview
The change in scores of the angina frequency dimension of the Seattle Angina Questionnaire (SAQ) after 12 weeks therapy with ranolazine or placebo are presented. Change at 12 weeks was calculated as (Endpoint Value at 12 weeks - Endpoint Value at Baseline)/Endpoint Value at Baseline. Individual dimensions of the Seattle Angina Questionnaire are transformed to be a score from 0 to 100, where higher scores indicate better health. A positive number for the angina frequency dimension means that the participants are experiencing fewer episodes of angina at week 12 than they were at the baseline visit.
COMPLETED
PHASE2
26 participants
Baseline, Week 12
2019-05-21
Participant Flow
Participants were recruited from Emory University Hospital in Atlanta, Georgia. Participant enrollment began in September 2014 and all study procedures were completed in June 2018.
Participant milestones
| Measure |
Ranolazine
Participants receiving 500mg twice a day for 2 weeks then 1000mg twice daily of ranolazine for 10 weeks
|
Placebo
Participants receiving a placebo to match the ranolazine dose for 12 weeks
|
|---|---|---|
|
Overall Study
STARTED
|
13
|
13
|
|
Overall Study
COMPLETED
|
11
|
11
|
|
Overall Study
NOT COMPLETED
|
2
|
2
|
Reasons for withdrawal
| Measure |
Ranolazine
Participants receiving 500mg twice a day for 2 weeks then 1000mg twice daily of ranolazine for 10 weeks
|
Placebo
Participants receiving a placebo to match the ranolazine dose for 12 weeks
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
2
|
2
|
Baseline Characteristics
Microvascular Assessment of Ranolazine in Non-Obstructive Atherosclerosis (MARINA)
Baseline characteristics by cohort
| Measure |
Ranolazine
n=11 Participants
Participants receiving 500mg twice a day for 2 weeks then 1000mg twice daily of ranolazine for 10 weeks
|
Placebo
n=11 Participants
Participants receiving a placebo to match the ranolazine dose for 12 weeks
|
Total
n=22 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
54.6 years
STANDARD_DEVIATION 12.3 • n=5 Participants
|
51.9 years
STANDARD_DEVIATION 13.9 • n=7 Participants
|
53 years
STANDARD_DEVIATION 12 • n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
8 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African American
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
11 participants
n=5 Participants
|
11 participants
n=7 Participants
|
22 participants
n=5 Participants
|
|
Hypertension
|
8 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Prior myocardial infarction
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 12The change in scores of the angina frequency dimension of the Seattle Angina Questionnaire (SAQ) after 12 weeks therapy with ranolazine or placebo are presented. Change at 12 weeks was calculated as (Endpoint Value at 12 weeks - Endpoint Value at Baseline)/Endpoint Value at Baseline. Individual dimensions of the Seattle Angina Questionnaire are transformed to be a score from 0 to 100, where higher scores indicate better health. A positive number for the angina frequency dimension means that the participants are experiencing fewer episodes of angina at week 12 than they were at the baseline visit.
Outcome measures
| Measure |
Ranolazine
n=11 Participants
Participants receiving 500mg twice a day for 2 weeks then 1000mg twice daily of ranolazine for 10 weeks
|
Placebo
n=11 Participants
Participants receiving a placebo to match the ranolazine dose for 12 weeks
|
|---|---|---|
|
Change in Seattle Angina Questionnaire Score Regarding Angina Frequency
|
0.70 score on a scale
Standard Deviation 1.26
|
0.27 score on a scale
Standard Deviation 0.62
|
SECONDARY outcome
Timeframe: Baseline, Week 12The change in scores of the physical limitation dimension of the Seattle Angina Questionnaire (SAQ) after 12 weeks therapy with ranolazine or placebo are presented. Change at 12 weeks was calculated as (Endpoint Value at 12 weeks - Endpoint Value at Baseline)/Endpoint Value at Baseline. Individual dimensions of the Seattle Angina Questionnaire are transformed to be a score from 0 to 100, where higher scores indicate better health. A positive number for the physical limitation dimension means that the participants are experiencing less limitation at week 12 than they were at the baseline visit.
Outcome measures
| Measure |
Ranolazine
n=11 Participants
Participants receiving 500mg twice a day for 2 weeks then 1000mg twice daily of ranolazine for 10 weeks
|
Placebo
n=11 Participants
Participants receiving a placebo to match the ranolazine dose for 12 weeks
|
|---|---|---|
|
Change in Seattle Angina Questionnaire Score Regarding Physical Limitation
|
-0.09 score on a scale
Standard Deviation 0.25
|
0.27 score on a scale
Standard Deviation 0.68
|
SECONDARY outcome
Timeframe: Baseline, Week 12The change in scores of the angina stability dimension of the Seattle Angina Questionnaire (SAQ) after 12 weeks therapy with ranolazine or placebo are presented. Change at 12 weeks was calculated as (Endpoint Value at 12 weeks - Endpoint Value at Baseline)/Endpoint Value at Baseline. Individual dimensions of the Seattle Angina Questionnaire are transformed to be a score from 0 to 100, where higher scores indicate better health. A positive number for the angina stability dimension means that the participants are experiencing fewer changes in their angina at week 12 than they were at the baseline visit.
Outcome measures
| Measure |
Ranolazine
n=11 Participants
Participants receiving 500mg twice a day for 2 weeks then 1000mg twice daily of ranolazine for 10 weeks
|
Placebo
n=11 Participants
Participants receiving a placebo to match the ranolazine dose for 12 weeks
|
|---|---|---|
|
Change in Seattle Angina Questionnaire Score Regarding Angina Stability
|
0.00 score on a scale
Standard Deviation 0.79
|
0.50 score on a scale
Standard Deviation 1.16
|
SECONDARY outcome
Timeframe: Baseline, Week 12The change in scores of the treatment satisfaction dimension of the Seattle Angina Questionnaire (SAQ) after 12 weeks therapy with ranolazine or placebo are presented. Change at 12 weeks was calculated as (Endpoint Value at 12 weeks - Endpoint Value at Baseline)/Endpoint Value at Baseline. Individual dimensions of the Seattle Angina Questionnaire are transformed to be a score from 0 to 100, where higher scores indicate better health. A positive number for the treatment satisfaction dimension means that the participants are experiencing greater satisfaction with their treatment at week 12 than they were at the baseline visit.
Outcome measures
| Measure |
Ranolazine
n=11 Participants
Participants receiving 500mg twice a day for 2 weeks then 1000mg twice daily of ranolazine for 10 weeks
|
Placebo
n=11 Participants
Participants receiving a placebo to match the ranolazine dose for 12 weeks
|
|---|---|---|
|
Change in Seattle Angina Questionnaire Score Regarding Treatment Satisfaction
|
1.17 score on a scale
Standard Deviation 3.92
|
0.28 score on a scale
Standard Deviation 0.49
|
SECONDARY outcome
Timeframe: Baseline, Week 12The change in scores of the disease perception dimension of the Seattle Angina Questionnaire (SAQ) after 12 weeks therapy with ranolazine or placebo are presented. Change at 12 weeks was calculated as (Endpoint Value at 12 weeks - Endpoint Value at Baseline)/Endpoint Value at Baseline. Individual dimensions of the Seattle Angina Questionnaire are transformed to be a score from 0 to 100, where higher scores indicate better health. A positive number for the disease perception dimension means that the participants felt that their disease impacted their quality of life less at week 12 than at the baseline visit.
Outcome measures
| Measure |
Ranolazine
n=11 Participants
Participants receiving 500mg twice a day for 2 weeks then 1000mg twice daily of ranolazine for 10 weeks
|
Placebo
n=11 Participants
Participants receiving a placebo to match the ranolazine dose for 12 weeks
|
|---|---|---|
|
Change in Seattle Angina Questionnaire Score Regarding Disease Perception
|
0.89 score on a scale
Standard Deviation 1.49
|
1.00 score on a scale
Standard Deviation 0.99
|
SECONDARY outcome
Timeframe: Baseline, Week 12The change in VO2, as measured by cardiopulmonary exercise testing (CPET), after 12 weeks therapy with ranolazine compared with placebo. VO2 max is the maximum amount of oxygen the participants are utilizing during intense treatment. To standardize exercise stress testing, CPET was performed under the guidance of the MET-TEST CPET network in Atlanta, Georgia. The MET-TEST was created in 2003 and is a high-precision stress test with detailed physiological assessment, allowing accurate and reproducible measurements of peak VO2. Individuals may demonstrate an abnormal CPET response before they develop symptoms or present with cardiac events and abnormal CPET results are strong predictors of future adverse outcomes. Higher VO2 values indicate better oxygen utility and positive value for VO2 change means there was improvement from baseline at the week 12 visit. Change at 12 weeks was calculated as (Endpoint Value at 12 weeks - Endpoint Value at Baseline)/Endpoint Value at Baseline.
Outcome measures
| Measure |
Ranolazine
n=11 Participants
Participants receiving 500mg twice a day for 2 weeks then 1000mg twice daily of ranolazine for 10 weeks
|
Placebo
n=11 Participants
Participants receiving a placebo to match the ranolazine dose for 12 weeks
|
|---|---|---|
|
Change in Peak Rate of Oxygen Consumption (VO2 Max)
|
-0.03 L/min
Standard Deviation 0.23
|
0.06 L/min
Standard Deviation 0.11
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: Data for this outcome measure was not collected.
Change in time to angina as measured by cardiopulmonary exercise testing after 12 weeks therapy with Ranolazine compared with placebo. Change at 12 weeks was calculated as (Endpoint Value at 12 weeks - Endpoint Value at Baseline)/Endpoint Value at Baseline.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Week 12Change in exercise was measured as Metabolic Equivalents of Task (METs) at Peak by cardiopulmonary exercise testing (CPET) after 12 weeks therapy with ranolazine compared with placebo. METs are used to describe functional aerobic capacity and harder physical tasks require a higher number of METs. METs at a peak level of exercise was determined for each participant. Change at 12 weeks was calculated as (Endpoint Value at 12 weeks - Endpoint Value at Baseline)/Endpoint Value at Baseline. A positive value for change in METs at Peak of exercise indicates that the participant has improved their aerobic capacity from baseline at the week 12 visit.
Outcome measures
| Measure |
Ranolazine
n=11 Participants
Participants receiving 500mg twice a day for 2 weeks then 1000mg twice daily of ranolazine for 10 weeks
|
Placebo
n=11 Participants
Participants receiving a placebo to match the ranolazine dose for 12 weeks
|
|---|---|---|
|
Change in Metabolic Equivalents of Task (METs) at Peak
|
0.00 3.5ml of oxygen/kg per min
Standard Deviation 0.20
|
4.42 3.5ml of oxygen/kg per min
Standard Deviation 14.45
|
SECONDARY outcome
Timeframe: Baseline, Week 12The changes in Coronary Flow Reserve (CFR) after 12 weeks therapy with ranolazine compared with placebo are presented here. CFR is a measurement of the maximum increase of blood flow through the coronary arteries during exercise. Average peak velocity (APV) was assessed over a 3- to 5-beats period. CFR was defined as the ratio of hyperemic to basal APV. A low CFR is an indication of coronary artery disease. Change at 12 weeks was calculated as (Endpoint Value at 12 weeks - Endpoint Value at Baseline)/Endpoint Value at Baseline. A positive value for the change in CFR suggests improvement in coronary artery blood flow between the baseline and week 12 visits.
Outcome measures
| Measure |
Ranolazine
n=11 Participants
Participants receiving 500mg twice a day for 2 weeks then 1000mg twice daily of ranolazine for 10 weeks
|
Placebo
n=11 Participants
Participants receiving a placebo to match the ranolazine dose for 12 weeks
|
|---|---|---|
|
Change in Coronary Flow Reserve (CFR)
|
0.38 ratio of hyperemic to basal APV
Standard Deviation 0.85
|
0.09 ratio of hyperemic to basal APV
Standard Deviation 0.30
|
SECONDARY outcome
Timeframe: Baseline, Week 12Change in Hyperemic Microcirculatory Resistance (HMR) after 12 weeks therapy with ranolazine compared with placebo. Average peak velocity (APV) was assessed over a 3- to 5-beats period. HMR was measured as the ratio of distal pressure to APV. Change at 12 weeks was calculated as (Endpoint Value at 12 weeks - Endpoint Value at Baseline)/Endpoint Value at Baseline. Higher HMR is associated with myocardial ischemia and a positive value for change in HMR indicates increased risk for cardiac events at the week 12 visit.
Outcome measures
| Measure |
Ranolazine
n=11 Participants
Participants receiving 500mg twice a day for 2 weeks then 1000mg twice daily of ranolazine for 10 weeks
|
Placebo
n=11 Participants
Participants receiving a placebo to match the ranolazine dose for 12 weeks
|
|---|---|---|
|
Change in Hyperemic Microcirculatory Resistance (HMR)
|
0.14 mmHg/cm/s
Standard Deviation 0.50
|
-0.04 mmHg/cm/s
Standard Deviation 0.42
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: Data for this outcome measure was not collected.
Coronary endothelial function will also be evaluated by measurement of coronary blood flow during infusion of intracoronary acetylcholine. Coronary blood flow (CBF) is defined as diameter (D)2 x APV / 8. Percent change in CBF (%ΔCBF) is calculated by (CBFACh - CBFbaseline) / CBFbaseline x 100%, where a \>50% increase in CBF in response to acetylcholine is considered normal.
Outcome measures
Outcome data not reported
Adverse Events
Ranolazine
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place