Trial Outcomes & Findings for Impact of Chronic Kidney Disease on the Effects of Ticagrelor in Patients With Diabetes and Coronary Artery Disease (NCT NCT02539160)
NCT ID: NCT02539160
Last Updated: 2022-01-28
Results Overview
The primary end point of the study was platelet reactivity assessed by VASP-PRI following treatment with ticagrelor 90mg between DM-CKD and DM-non-CKD cohorts. PRI % is a measure of platelet reactivity, where higher PRI levels represent higher platelet reactivity and lower effect of antiplatelet medications. PRI greater than 50% represents inadequate response to antiplatelet medications.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
101 participants
Primary outcome timeframe
7 days
Results posted on
2022-01-28
Participant Flow
Subjects were recruited between February 2016 and November 2019 at the outpatient clinics of University of Florida Health - Jacksonville (Jacksonville, Florida, USA).
101 patients were consented and enrolled in the study; 9 patients were not eligible for randomization due to the presence of exclusion criteria. A total of 92 patients (non-CKD, n=48; CKD, n=44) were randomized and exposed to at least one dose of study medication.
Participant milestones
| Measure |
DM-Non-CKD Ticagrelor 90 First
Patients with diabetes mellitus (DM) and coronary artery disease (CAD) were stratified according to chronic kidney disease (CKD) status. Non-CKD was defined by a glomerular filtrate rate (GFR) ≥ 60 ml/min/1.73m2.
Non-CKD patients were randomized 1:1 to a) standard dose ticagrelor (90mg twice daily) for 7-10 days or b) low dose ticagrelor (60mg twice daily) for 7-10 days (phase 1). After 7-10 days of randomized treatment patients were crossed over to the alternative treatment, which was maintained for additional 7-10 days (phase 2).No wash out was performed.
|
DM-Non-CKD Ticagrelor 60 First
Patients with diabetes mellitus (DM) and coronary artery disease (CAD) were stratified according to chronic kidney disease (CKD) status. CKD was defined by a glomerular filtrate rate (GFR) \< 60 ml/min/1.73m2.
CKD patients were randomized 1:1 to a) standard dose ticagrelor (90mg twice daily) for 7-10 days or b) low dose ticagrelor (60mg twice daily) for 7-10 days (phase 1). After 7-10 days of randomized treatment patients were crossed over to the alternative treatment, which was maintained for additional 7-10 days (phase 2). No wash out was performed.
|
DM-CKD Ticagrelor 90 First
Patients with diabetes mellitus (DM) and coronary artery disease (CAD) were stratified according to chronic kidney disease (CKD) status. CKD was defined by a glomerular filtrate rate (GFR) \< 60 ml/min/1.73m2.
CKD patients were randomized 1:1 to a) standard dose ticagrelor (90mg twice daily) for 7-10 days or b) low dose ticagrelor (60mg twice daily) for 7-10 days (phase 1). After 7-10 days of randomized treatment patients were crossed over to the alternative treatment, which was maintained for additional 7-10 days (phase 2). No wash out was performed.
|
DM-CKD Ticagrelor 60 First
Patients with diabetes mellitus (DM) and coronary artery disease (CAD) were stratified according to chronic kidney disease (CKD) status. CKD was defined by a glomerular filtrate rate (GFR) \< 60 ml/min/1.73m2.
CKD patients were randomized 1:1 to a) standard dose ticagrelor (90mg twice daily) for 7-10 days or b) low dose ticagrelor (60mg twice daily) for 7-10 days (phase 1). After 7-10 days of randomized treatment patients were crossed over to the alternative treatment, which was maintained for additional 7-10 days (phase 2). No wash out was performed.
|
|---|---|---|---|---|
|
Phase 1 Pre-crossover
STARTED
|
24
|
24
|
22
|
22
|
|
Phase 1 Pre-crossover
COMPLETED
|
19
|
20
|
19
|
19
|
|
Phase 1 Pre-crossover
NOT COMPLETED
|
5
|
4
|
3
|
3
|
|
Phase 2 Post-crossover
STARTED
|
19
|
20
|
19
|
19
|
|
Phase 2 Post-crossover
COMPLETED
|
19
|
20
|
19
|
19
|
|
Phase 2 Post-crossover
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
DM-Non-CKD Ticagrelor 90 First
Patients with diabetes mellitus (DM) and coronary artery disease (CAD) were stratified according to chronic kidney disease (CKD) status. Non-CKD was defined by a glomerular filtrate rate (GFR) ≥ 60 ml/min/1.73m2.
Non-CKD patients were randomized 1:1 to a) standard dose ticagrelor (90mg twice daily) for 7-10 days or b) low dose ticagrelor (60mg twice daily) for 7-10 days (phase 1). After 7-10 days of randomized treatment patients were crossed over to the alternative treatment, which was maintained for additional 7-10 days (phase 2).No wash out was performed.
|
DM-Non-CKD Ticagrelor 60 First
Patients with diabetes mellitus (DM) and coronary artery disease (CAD) were stratified according to chronic kidney disease (CKD) status. CKD was defined by a glomerular filtrate rate (GFR) \< 60 ml/min/1.73m2.
CKD patients were randomized 1:1 to a) standard dose ticagrelor (90mg twice daily) for 7-10 days or b) low dose ticagrelor (60mg twice daily) for 7-10 days (phase 1). After 7-10 days of randomized treatment patients were crossed over to the alternative treatment, which was maintained for additional 7-10 days (phase 2). No wash out was performed.
|
DM-CKD Ticagrelor 90 First
Patients with diabetes mellitus (DM) and coronary artery disease (CAD) were stratified according to chronic kidney disease (CKD) status. CKD was defined by a glomerular filtrate rate (GFR) \< 60 ml/min/1.73m2.
CKD patients were randomized 1:1 to a) standard dose ticagrelor (90mg twice daily) for 7-10 days or b) low dose ticagrelor (60mg twice daily) for 7-10 days (phase 1). After 7-10 days of randomized treatment patients were crossed over to the alternative treatment, which was maintained for additional 7-10 days (phase 2). No wash out was performed.
|
DM-CKD Ticagrelor 60 First
Patients with diabetes mellitus (DM) and coronary artery disease (CAD) were stratified according to chronic kidney disease (CKD) status. CKD was defined by a glomerular filtrate rate (GFR) \< 60 ml/min/1.73m2.
CKD patients were randomized 1:1 to a) standard dose ticagrelor (90mg twice daily) for 7-10 days or b) low dose ticagrelor (60mg twice daily) for 7-10 days (phase 1). After 7-10 days of randomized treatment patients were crossed over to the alternative treatment, which was maintained for additional 7-10 days (phase 2). No wash out was performed.
|
|---|---|---|---|---|
|
Phase 1 Pre-crossover
Adverse Event
|
3
|
3
|
2
|
1
|
|
Phase 1 Pre-crossover
Withdrawal by Subject
|
2
|
1
|
1
|
0
|
|
Phase 1 Pre-crossover
Protocol Violation
|
0
|
0
|
0
|
2
|
Baseline Characteristics
Impact of Chronic Kidney Disease on the Effects of Ticagrelor in Patients With Diabetes and Coronary Artery Disease
Baseline characteristics by cohort
| Measure |
DM-Non-CKD (All Participants Regardless of Sequence)
n=39 Participants
Patients with diabetes mellitus (DM) and coronary artery disease (CAD) were stratified according to chronic kidney disease (CKD) status. Non-CKD was defined by a glomerular filtrate rate (GFR) ≥ 60 ml/min/1.73m2.
Non-CKD patients were randomized 1:1 to a) standard dose ticagrelor (90mg twice daily) for 7-10 days or b) low dose ticagrelor (60mg twice daily) for 7-10 days (phase 1). After 7-10 days of randomized treatment patients were crossed over to the alternative treatment, which was maintained for additional 7-10 days (phase 2).
This is a crossover study where participants in each cohort received both treatments but in difference sequences. Therefore, baseline characteristics are presented for the two separate cohorts but combining patients together regardless of treatment sequence.
|
DM-CKD (All Participants Regardless of Sequence)
n=38 Participants
Patients with diabetes mellitus (DM) and coronary artery disease (CAD) were stratified according to chronic kidney disease (CKD) status. CKD was defined by a glomerular filtrate rate (GFR) \< 60 ml/min/1.73m2.
CKD patients were randomized 1:1 to a) standard dose ticagrelor (90mg twice daily) for 7-10 days or b) low dose ticagrelor (60mg twice daily) for 7-10 days (phase 1). After 7-10 days of randomized treatment patients were crossed over to the alternative treatment, which was maintained for additional 7-10 days (phase 2).
This is a crossover study where participants in each cohort received both treatments but in difference sequences. Therefore, baseline characteristics are presented for the two separate cohorts but combining patients together regardless of treatment sequence.
|
Total
n=77 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
62 years
STANDARD_DEVIATION 8 • n=5 Participants
|
66 years
STANDARD_DEVIATION 9 • n=7 Participants
|
64 years
STANDARD_DEVIATION 8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
25 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
48 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
15 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
20 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
4 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
GFR
|
88 ml/min/1.73m^2
STANDARD_DEVIATION 17 • n=5 Participants
|
46 ml/min/1.73m^2
STANDARD_DEVIATION 9 • n=7 Participants
|
67 ml/min/1.73m^2
STANDARD_DEVIATION 25 • n=5 Participants
|
|
Prior myocardial infarction
|
18 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
41 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 7 daysPopulation: The pharmacodynamic (PD) population included all patients with any PD data on study drug and without a major protocol deviation thought to affect significantly the PD findings. The PD population was used for analysis of all primary and secondary PD variables.
The primary end point of the study was platelet reactivity assessed by VASP-PRI following treatment with ticagrelor 90mg between DM-CKD and DM-non-CKD cohorts. PRI % is a measure of platelet reactivity, where higher PRI levels represent higher platelet reactivity and lower effect of antiplatelet medications. PRI greater than 50% represents inadequate response to antiplatelet medications.
Outcome measures
| Measure |
CKD - Ticagrelor 90
n=38 Participants
Patients with chronic kidney disease will receive ticagrelor 90mg twice/daily for 7-10 days. Then patients will cross over to ticagrelor 60mg twice/daily for 7-10 days.
|
CKD - Ticagrelor 60
n=38 Participants
Patients with chronic kidney disease will receive ticagrelor 60mg twice/daily for 7-10 days. Then patients will cross over to ticagrelor 90mg twice/daily for 7-10 days.
|
Non-CKD - Ticagrelor 90
n=39 Participants
Patients without chronic kidney disease will receive ticagrelor 90mg twice/daily for 7-10 days. Then patients will cross over to ticagrelor 60mg twice/daily for 7-10 days.
|
Non-CKD - Ticagrelor 60
n=39 Participants
Patients without chronic kidney disease will receive ticagrelor 60mg twice/daily for 7-10 days. Then patients will cross over to ticagrelor 90mg twice/daily for 7-10 days.
|
|---|---|---|---|---|
|
Platelet Reactivity Measured by Vasodilator Stimulated Phosphoprotein (VASP) Platelet Reactivity Index (PRI %)
|
25 PRI%
Standard Deviation 14
|
32 PRI%
Standard Deviation 13
|
31 PRI%
Standard Deviation 20
|
38 PRI%
Standard Deviation 20
|
SECONDARY outcome
Timeframe: 7 daysPlatelet reactivity assessed by VerifyNow P2Y12 following treatment with ticagrelor 90mg or 60 mg between DM-CKD and DM-non-CKD cohorts. Results are expressed in P2Y12 reaction units (PRU). PRU is a measure of platelet reactivity, where higher PRU levels represent higher platelet reactivity and lower effect of antiplatelet medications. PRU greater than 208 represents inadequate response to antiplatelet medications.
Outcome measures
| Measure |
CKD - Ticagrelor 90
n=38 Participants
Patients with chronic kidney disease will receive ticagrelor 90mg twice/daily for 7-10 days. Then patients will cross over to ticagrelor 60mg twice/daily for 7-10 days.
|
CKD - Ticagrelor 60
n=38 Participants
Patients with chronic kidney disease will receive ticagrelor 60mg twice/daily for 7-10 days. Then patients will cross over to ticagrelor 90mg twice/daily for 7-10 days.
|
Non-CKD - Ticagrelor 90
n=39 Participants
Patients without chronic kidney disease will receive ticagrelor 90mg twice/daily for 7-10 days. Then patients will cross over to ticagrelor 60mg twice/daily for 7-10 days.
|
Non-CKD - Ticagrelor 60
n=39 Participants
Patients without chronic kidney disease will receive ticagrelor 60mg twice/daily for 7-10 days. Then patients will cross over to ticagrelor 90mg twice/daily for 7-10 days.
|
|---|---|---|---|---|
|
Platelet Reactivity Measured by VerifyNow P2Y12
|
39 PRU
Standard Deviation 57
|
59 PRU
Standard Deviation 56
|
51 PRU
Standard Deviation 52
|
74 PRU
Standard Deviation 65
|
Adverse Events
CKD - Ticagrelor 90
Serious events: 1 serious events
Other events: 9 other events
Deaths: 0 deaths
CKD - Ticagrelor 60
Serious events: 1 serious events
Other events: 6 other events
Deaths: 0 deaths
Non-CKD - Ticagrelor 90
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Non-CKD - Ticagrelor 60
Serious events: 1 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
CKD - Ticagrelor 90
n=38 participants at risk
Patients with chronic kidney disease will receive ticagrelor 90mg twice/daily for 7-10 days. Then patients will cross over to ticagrelor 60mg twice/daily for 7-10 days.
|
CKD - Ticagrelor 60
n=38 participants at risk
Patients with chronic kidney disease will receive ticagrelor 60mg twice/daily for 7-10 days. Then patients will cross over to ticagrelor 90mg twice/daily for 7-10 days.
|
Non-CKD - Ticagrelor 90
n=39 participants at risk
Patients without chronic kidney disease will receive ticagrelor 90mg twice/daily for 7-10 days. Then patients will cross over to ticagrelor 60mg twice/daily for 7-10 days.
|
Non-CKD - Ticagrelor 60
n=39 participants at risk
Patients without chronic kidney disease will receive ticagrelor 60mg twice/daily for 7-10 days. Then patients will cross over to ticagrelor 90mg twice/daily for 7-10 days.
|
|---|---|---|---|---|
|
Cardiac disorders
hypotension
|
0.00%
0/38 • Any adverse event during the study period (any time from enrollment until completion of the study, up to 20 days) was recorded.
|
2.6%
1/38 • Number of events 1 • Any adverse event during the study period (any time from enrollment until completion of the study, up to 20 days) was recorded.
|
0.00%
0/39 • Any adverse event during the study period (any time from enrollment until completion of the study, up to 20 days) was recorded.
|
0.00%
0/39 • Any adverse event during the study period (any time from enrollment until completion of the study, up to 20 days) was recorded.
|
|
Renal and urinary disorders
hypokalemia
|
0.00%
0/38 • Any adverse event during the study period (any time from enrollment until completion of the study, up to 20 days) was recorded.
|
0.00%
0/38 • Any adverse event during the study period (any time from enrollment until completion of the study, up to 20 days) was recorded.
|
0.00%
0/39 • Any adverse event during the study period (any time from enrollment until completion of the study, up to 20 days) was recorded.
|
2.6%
1/39 • Number of events 1 • Any adverse event during the study period (any time from enrollment until completion of the study, up to 20 days) was recorded.
|
|
Cardiac disorders
syncope
|
2.6%
1/38 • Number of events 1 • Any adverse event during the study period (any time from enrollment until completion of the study, up to 20 days) was recorded.
|
0.00%
0/38 • Any adverse event during the study period (any time from enrollment until completion of the study, up to 20 days) was recorded.
|
0.00%
0/39 • Any adverse event during the study period (any time from enrollment until completion of the study, up to 20 days) was recorded.
|
0.00%
0/39 • Any adverse event during the study period (any time from enrollment until completion of the study, up to 20 days) was recorded.
|
|
Metabolism and nutrition disorders
hyperglycemia
|
0.00%
0/38 • Any adverse event during the study period (any time from enrollment until completion of the study, up to 20 days) was recorded.
|
2.6%
1/38 • Number of events 1 • Any adverse event during the study period (any time from enrollment until completion of the study, up to 20 days) was recorded.
|
0.00%
0/39 • Any adverse event during the study period (any time from enrollment until completion of the study, up to 20 days) was recorded.
|
0.00%
0/39 • Any adverse event during the study period (any time from enrollment until completion of the study, up to 20 days) was recorded.
|
Other adverse events
| Measure |
CKD - Ticagrelor 90
n=38 participants at risk
Patients with chronic kidney disease will receive ticagrelor 90mg twice/daily for 7-10 days. Then patients will cross over to ticagrelor 60mg twice/daily for 7-10 days.
|
CKD - Ticagrelor 60
n=38 participants at risk
Patients with chronic kidney disease will receive ticagrelor 60mg twice/daily for 7-10 days. Then patients will cross over to ticagrelor 90mg twice/daily for 7-10 days.
|
Non-CKD - Ticagrelor 90
n=39 participants at risk
Patients without chronic kidney disease will receive ticagrelor 90mg twice/daily for 7-10 days. Then patients will cross over to ticagrelor 60mg twice/daily for 7-10 days.
|
Non-CKD - Ticagrelor 60
n=39 participants at risk
Patients without chronic kidney disease will receive ticagrelor 60mg twice/daily for 7-10 days. Then patients will cross over to ticagrelor 90mg twice/daily for 7-10 days.
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
minor bleeding
|
5.3%
2/38 • Number of events 2 • Any adverse event during the study period (any time from enrollment until completion of the study, up to 20 days) was recorded.
|
0.00%
0/38 • Any adverse event during the study period (any time from enrollment until completion of the study, up to 20 days) was recorded.
|
2.6%
1/39 • Number of events 1 • Any adverse event during the study period (any time from enrollment until completion of the study, up to 20 days) was recorded.
|
2.6%
1/39 • Number of events 1 • Any adverse event during the study period (any time from enrollment until completion of the study, up to 20 days) was recorded.
|
|
Respiratory, thoracic and mediastinal disorders
dyspnea
|
18.4%
7/38 • Number of events 7 • Any adverse event during the study period (any time from enrollment until completion of the study, up to 20 days) was recorded.
|
15.8%
6/38 • Number of events 6 • Any adverse event during the study period (any time from enrollment until completion of the study, up to 20 days) was recorded.
|
20.5%
8/39 • Number of events 8 • Any adverse event during the study period (any time from enrollment until completion of the study, up to 20 days) was recorded.
|
15.4%
6/39 • Number of events 6 • Any adverse event during the study period (any time from enrollment until completion of the study, up to 20 days) was recorded.
|
Additional Information
Dominick J. Angiolillo, MD, PhD
University of Florida College of Medicine Jacksonville
Phone: +1-904-244-3378
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place