Trial Outcomes & Findings for High Ticagrelor Loading Dose in STEMI (NCT NCT01898442)
NCT ID: NCT01898442
Last Updated: 2015-06-08
Results Overview
The primary end-point of the study was the comparison of the P2Y12 reaction units (PRU) determined by VerifyNow P2Y12 at 1 hour after administration
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
52 participants
Primary outcome timeframe
1 hour
Results posted on
2015-06-08
Participant Flow
Between September 2013 and June 2014.
There were a total of 129 STEMI activations; of these, 52 patients provided their written informed consent to participate in the study and were randomized.
Participant milestones
| Measure |
Ticagrelor 180mg
Standard ticagrelor 180mg loading dose
Ticagrelor 180mg: Randomization to standard ticagrelor loading dose
|
Ticagrelor 270mg
High ticagrelor 270mg loading dose
Ticagrelor 270mg: Randomization to a high ticagrelor loading dose regimen
|
Ticagrelor 360mg
High ticagrelor 360mg loading dose
Ticagrelor 360mg: Randomization to a high ticagrelor loading dose regimen
|
|---|---|---|---|
|
Overall Study
STARTED
|
17
|
17
|
18
|
|
Overall Study
COMPLETED
|
16
|
15
|
15
|
|
Overall Study
NOT COMPLETED
|
1
|
2
|
3
|
Reasons for withdrawal
| Measure |
Ticagrelor 180mg
Standard ticagrelor 180mg loading dose
Ticagrelor 180mg: Randomization to standard ticagrelor loading dose
|
Ticagrelor 270mg
High ticagrelor 270mg loading dose
Ticagrelor 270mg: Randomization to a high ticagrelor loading dose regimen
|
Ticagrelor 360mg
High ticagrelor 360mg loading dose
Ticagrelor 360mg: Randomization to a high ticagrelor loading dose regimen
|
|---|---|---|---|
|
Overall Study
Hemolysis/technical problems
|
1
|
2
|
2
|
|
Overall Study
Patient vomited pills
|
0
|
0
|
1
|
Baseline Characteristics
High Ticagrelor Loading Dose in STEMI
Baseline characteristics by cohort
| Measure |
Ticagrelor 180mg
n=16 Participants
Standard ticagrelor 180mg loading dose
Ticagrelor 180mg: Randomization to standard ticagrelor loading dose
|
Ticagrelor 270mg
n=15 Participants
High ticagrelor 270mg loading dose
Ticagrelor 270mg: Randomization to a high ticagrelor loading dose regimen
|
Ticagrelor 360mg
n=15 Participants
High ticagrelor 360mg loading dose
Ticagrelor 360mg: Randomization to a high ticagrelor loading dose regimen
|
Total
n=46 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
60 years
STANDARD_DEVIATION 8.6 • n=5 Participants
|
58 years
STANDARD_DEVIATION 8.5 • n=7 Participants
|
57 years
STANDARD_DEVIATION 12.1 • n=5 Participants
|
58 years
STANDARD_DEVIATION 9.5 • n=4 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
32 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 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
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
12 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
11 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
34 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 1 hourThe primary end-point of the study was the comparison of the P2Y12 reaction units (PRU) determined by VerifyNow P2Y12 at 1 hour after administration
Outcome measures
| Measure |
Ticagrelor 180mg
n=16 Participants
Standard ticagrelor 180mg loading dose
Ticagrelor 180mg: Randomization to standard ticagrelor loading dose
|
Ticagrelor 270mg
n=15 Participants
High ticagrelor 270mg loading dose
Ticagrelor 270mg: Randomization to a high ticagrelor loading dose regimen
|
Ticagrelor 360mg
n=15 Participants
High ticagrelor 360mg loading dose
Ticagrelor 360mg: Randomization to a high ticagrelor loading dose regimen
|
|---|---|---|---|
|
Platelet Reactivity by VerifyNow P2Y12
|
188 PRU
Standard Error 20
|
125 PRU
Standard Error 23
|
228 PRU
Standard Error 23
|
SECONDARY outcome
Timeframe: 30 min and 2, 4, 8, 24 hoursSecondary outcomes included the comparison of the P2Y12 reaction units (PRU) determined by VerifyNow P2Y12 at 30 min and 2, 4, 8, 24 hours after ticagrelor loading dose administration
Outcome measures
| Measure |
Ticagrelor 180mg
n=16 Participants
Standard ticagrelor 180mg loading dose
Ticagrelor 180mg: Randomization to standard ticagrelor loading dose
|
Ticagrelor 270mg
n=15 Participants
High ticagrelor 270mg loading dose
Ticagrelor 270mg: Randomization to a high ticagrelor loading dose regimen
|
Ticagrelor 360mg
n=15 Participants
High ticagrelor 360mg loading dose
Ticagrelor 360mg: Randomization to a high ticagrelor loading dose regimen
|
|---|---|---|---|
|
Platelet Reactivity by VerifyNow P2Y12 at Other Time Points
30 min
|
231 PRU
Standard Error 15
|
225 PRU
Standard Error 17
|
249 PRU
Standard Error 17
|
|
Platelet Reactivity by VerifyNow P2Y12 at Other Time Points
2 hours
|
90 PRU
Standard Error 28
|
83 PRU
Standard Error 31
|
148 PRU
Standard Error 31
|
|
Platelet Reactivity by VerifyNow P2Y12 at Other Time Points
4 hours
|
75 PRU
Standard Error 19
|
46 PRU
Standard Error 22
|
69 PRU
Standard Error 22
|
|
Platelet Reactivity by VerifyNow P2Y12 at Other Time Points
8 hours
|
60 PRU
Standard Error 18
|
44 PRU
Standard Error 21
|
78 PRU
Standard Error 21
|
|
Platelet Reactivity by VerifyNow P2Y12 at Other Time Points
24 hours
|
39 PRU
Standard Error 13
|
41 PRU
Standard Error 14
|
72 PRU
Standard Error 14
|
SECONDARY outcome
Timeframe: 30 min and 1, 2, 4, 8, 24 hoursSecondary outcomes included the comparison of the platelet reactivity index (PRI) determined by vasodilator-stimulated phosphoprotein (VASP) at 30 min and 1, 2, 4, 8, 24 hours after ticagrelor loading dose administration
Outcome measures
| Measure |
Ticagrelor 180mg
n=16 Participants
Standard ticagrelor 180mg loading dose
Ticagrelor 180mg: Randomization to standard ticagrelor loading dose
|
Ticagrelor 270mg
n=15 Participants
High ticagrelor 270mg loading dose
Ticagrelor 270mg: Randomization to a high ticagrelor loading dose regimen
|
Ticagrelor 360mg
n=15 Participants
High ticagrelor 360mg loading dose
Ticagrelor 360mg: Randomization to a high ticagrelor loading dose regimen
|
|---|---|---|---|
|
Platelet Reactivity by Vasodilator-stimulated Phosphoprotein (VASP) at All Time Points
30 min
|
76 PRI
Standard Error 6
|
81 PRI
Standard Error 6
|
78 PRI
Standard Error 6
|
|
Platelet Reactivity by Vasodilator-stimulated Phosphoprotein (VASP) at All Time Points
1 hour
|
56 PRI
Standard Error 7
|
51 PRI
Standard Error 8
|
78 PRI
Standard Error 8
|
|
Platelet Reactivity by Vasodilator-stimulated Phosphoprotein (VASP) at All Time Points
2 hours
|
41 PRI
Standard Error 9
|
39 PRI
Standard Error 10
|
48 PRI
Standard Error 10
|
|
Platelet Reactivity by Vasodilator-stimulated Phosphoprotein (VASP) at All Time Points
4 hours
|
35 PRI
Standard Error 6
|
30 PRI
Standard Error 7
|
21 PRI
Standard Error 7
|
|
Platelet Reactivity by Vasodilator-stimulated Phosphoprotein (VASP) at All Time Points
8 hours
|
25 PRI
Standard Error 5
|
30 PRI
Standard Error 5
|
23 PRI
Standard Error 5
|
|
Platelet Reactivity by Vasodilator-stimulated Phosphoprotein (VASP) at All Time Points
24 hours
|
27 PRI
Standard Error 4
|
30 PRI
Standard Error 5
|
28 PRI
Standard Error 5
|
SECONDARY outcome
Timeframe: 24 hoursPharmacokinetic assessments included determination of plasma concentration of ticagrelor. Time for the maximum plasma concentration (Tmax), maximum observed plasma concentration (Cmax) and the area under the plasma concentration vs. time curve from time 0 to the last measurable concentration (AUC0-t) were calculated.
Outcome measures
| Measure |
Ticagrelor 180mg
n=16 Participants
Standard ticagrelor 180mg loading dose
Ticagrelor 180mg: Randomization to standard ticagrelor loading dose
|
Ticagrelor 270mg
n=15 Participants
High ticagrelor 270mg loading dose
Ticagrelor 270mg: Randomization to a high ticagrelor loading dose regimen
|
Ticagrelor 360mg
n=15 Participants
High ticagrelor 360mg loading dose
Ticagrelor 360mg: Randomization to a high ticagrelor loading dose regimen
|
|---|---|---|---|
|
Pharmacokinetic Profiles of Ticagrelor (Tmax)
|
3.9 hours
Interval 2.0 to 24.0
|
5.0 hours
Interval 1.0 to 24.0
|
7.4 hours
Interval 2.0 to 24.0
|
SECONDARY outcome
Timeframe: 24 hoursPharmacokinetic assessments included determination of plasma concentration of ticagrelor. Time for the maximum plasma concentration (Tmax), maximum observed plasma concentration (Cmax) and the area under the plasma concentration vs. time curve from time 0 to the last measurable concentration (AUC0-t) were calculated.
Outcome measures
| Measure |
Ticagrelor 180mg
n=16 Participants
Standard ticagrelor 180mg loading dose
Ticagrelor 180mg: Randomization to standard ticagrelor loading dose
|
Ticagrelor 270mg
n=15 Participants
High ticagrelor 270mg loading dose
Ticagrelor 270mg: Randomization to a high ticagrelor loading dose regimen
|
Ticagrelor 360mg
n=15 Participants
High ticagrelor 360mg loading dose
Ticagrelor 360mg: Randomization to a high ticagrelor loading dose regimen
|
|---|---|---|---|
|
Pharmacokinetic Profiles of Ticagrelor (Cmax)
|
789 ng/mL
Interval 95.0 to 3550.0
|
1208 ng/mL
Interval 276.0 to 2940.0
|
1208 ng/mL
Interval 242.0 to 4040.0
|
SECONDARY outcome
Timeframe: 24 hoursPharmacokinetic assessments included determination of plasma concentration of ticagrelor. Time for the maximum plasma concentration (Tmax), maximum observed plasma concentration (Cmax) and the area under the plasma concentration vs. time curve from time 0 to the last measurable concentration (AUC0-t) were calculated.
Outcome measures
| Measure |
Ticagrelor 180mg
n=16 Participants
Standard ticagrelor 180mg loading dose
Ticagrelor 180mg: Randomization to standard ticagrelor loading dose
|
Ticagrelor 270mg
n=15 Participants
High ticagrelor 270mg loading dose
Ticagrelor 270mg: Randomization to a high ticagrelor loading dose regimen
|
Ticagrelor 360mg
n=15 Participants
High ticagrelor 360mg loading dose
Ticagrelor 360mg: Randomization to a high ticagrelor loading dose regimen
|
|---|---|---|---|
|
Pharmacokinetic Profiles of Ticagrelor (AUC0-t)
|
7893 ng*hr/mL
Interval 1270.0 to 33974.0
|
12379 ng*hr/mL
Interval 2935.0 to 33105.0
|
12381 ng*hr/mL
Interval 768.0 to 66201.0
|
Adverse Events
Ticagrelor 180mg
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Ticagrelor 270mg
Serious events: 1 serious events
Other events: 1 other events
Deaths: 0 deaths
Ticagrelor 360mg
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Ticagrelor 180mg
n=17 participants at risk
Standard ticagrelor 180mg loading dose
Ticagrelor 180mg: Randomization to standard ticagrelor loading dose
|
Ticagrelor 270mg
n=17 participants at risk
High ticagrelor 270mg loading dose
Ticagrelor 270mg: Randomization to a high ticagrelor loading dose regimen
|
Ticagrelor 360mg
n=18 participants at risk
High ticagrelor 360mg loading dose
Ticagrelor 360mg: Randomization to a high ticagrelor loading dose regimen
|
|---|---|---|---|
|
Vascular disorders
Ischemic stroke
|
0.00%
0/17 • In-hospital adverse events, including ischemic events, bleeding, bradyarrhythmias, and dyspnea, defined according to previously reported criteria in the PLATO trial, were recorded.
|
5.9%
1/17 • Number of events 1 • In-hospital adverse events, including ischemic events, bleeding, bradyarrhythmias, and dyspnea, defined according to previously reported criteria in the PLATO trial, were recorded.
|
0.00%
0/18 • In-hospital adverse events, including ischemic events, bleeding, bradyarrhythmias, and dyspnea, defined according to previously reported criteria in the PLATO trial, were recorded.
|
|
Vascular disorders
Major-life threatening bleed
|
0.00%
0/17 • In-hospital adverse events, including ischemic events, bleeding, bradyarrhythmias, and dyspnea, defined according to previously reported criteria in the PLATO trial, were recorded.
|
0.00%
0/17 • In-hospital adverse events, including ischemic events, bleeding, bradyarrhythmias, and dyspnea, defined according to previously reported criteria in the PLATO trial, were recorded.
|
5.6%
1/18 • Number of events 1 • In-hospital adverse events, including ischemic events, bleeding, bradyarrhythmias, and dyspnea, defined according to previously reported criteria in the PLATO trial, were recorded.
|
Other adverse events
| Measure |
Ticagrelor 180mg
n=17 participants at risk
Standard ticagrelor 180mg loading dose
Ticagrelor 180mg: Randomization to standard ticagrelor loading dose
|
Ticagrelor 270mg
n=17 participants at risk
High ticagrelor 270mg loading dose
Ticagrelor 270mg: Randomization to a high ticagrelor loading dose regimen
|
Ticagrelor 360mg
n=18 participants at risk
High ticagrelor 360mg loading dose
Ticagrelor 360mg: Randomization to a high ticagrelor loading dose regimen
|
|---|---|---|---|
|
Vascular disorders
Minimal/minor bleeding
|
11.8%
2/17 • Number of events 2 • In-hospital adverse events, including ischemic events, bleeding, bradyarrhythmias, and dyspnea, defined according to previously reported criteria in the PLATO trial, were recorded.
|
5.9%
1/17 • Number of events 1 • In-hospital adverse events, including ischemic events, bleeding, bradyarrhythmias, and dyspnea, defined according to previously reported criteria in the PLATO trial, were recorded.
|
0.00%
0/18 • In-hospital adverse events, including ischemic events, bleeding, bradyarrhythmias, and dyspnea, defined according to previously reported criteria in the PLATO trial, were recorded.
|
Additional Information
Dominick J. Angiolillo, MD, PhD
University of Florida - Jacksonville
Phone: 9042443933
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place