Non-ST or ST Elevation Acute Coronary Syndromes
Conditions
Keywords
Non-ST or ST Elevation Acute Coronary Syndromes, Ticagrelor, Clopidogrel, Antiplatelet Effect
Brief summary
The purpose of this study is to test the hypothesis that the onset of the antiplatelet effect of ticagrelor is more rapid and greater than clopidogrel in Chinese patients with ACS.
Interventions
DRUGTicagrelor
90mg tablets. loading dose of 180mg ticagrelor tablets (two 90mg tablets) taken orally, followed by 90mg of ticagrelor 12 hours after the first dose. Duration of treatment: 6 weeks.
DRUGClopidogrel
75mg capsule. loading dose of 600mg clopidogrel capsules (eight 75mg capsules) taken orally, follow by 75mg of clopidogrel capsules orally od. Duration of treatment: 6 weeks.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 1\. Provision of informed consent prior to any study specific procedures * 2\. Female or male aged at least 18 years * 3\. Females of child-bearing potential must have a negative urine pregnancy test at enrolment and be willing to use reliable contraception * 4\. Index event of non-ST or ST segment elevation ACS.
Exclusion criteria
* 1.Contraindication or other reason that clopidogrel or ticagrelor should not be administered (eg, hypersensitivity, active bleeding, moderate or severe liver disease, history of previous intracranial bleed, GI bleed within the past 6 months, major surgery within 30 days) * 2\. Oral anticoagulation therapy or GP IIb/IIIa receptor antagonists therapy within 30 days prior to randomisation or cannot be stopped * 3\. Ticagrelor or clopidogrel or other P2Y12 inhibitors within 14 days prior to randomisation * 4\. Requires dialysis * 5\. Nonselective non-steroidal anti-inflammatory drugs (NSAIDs) and prostacyclins (PGI2) therapy that cannot be stopped
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| the Percentage Inhibition of the P2Y12 Receptor | at 2 hours after first dose of study drug | Note: the primary endpoint was changed per the statistical analysis plan prior database lock. |
Secondary
| Measure | Time frame |
|---|---|
| the Percentage Inhibition of the P2Y12 Receptor | at 0.5 hour after first dose of study drug |
Countries
China
Participant flow
Recruitment details
First subject enrolled: 15/05/2013, Last subject last visit: 18/03/2014. There were 5 study centers in China, which participated this study.
Pre-assignment details
There was no run-in or any other pre-assignment periods following participant enrollment.
Participants by arm
| Arm | Count |
|---|---|
| Ticagrelor Patients received a loading dose of 180mg ticagrelor tablets (two 90mg tablets) taken orally, followed by 90mg of ticagrelor 12 hours after the first dose. The third dose of ticagrelor was given to patients after the blood sample had been obtained 24 hours after the first dose. Thereafter, the patients took 90mg of ticagrelor orally bd. The total study period was 6 weeks. | 28 |
| Clopidogrel Patients received a loading dose of 600mg clopidogrel tablets (eight 75mg tablets) taken orally. The second dose of clopidogrel had been given to patients after the blood sample had been obtained 24 hours after the first dose. Thereafter, the patients took 75mg of clopidogrel orally od. The total study period was 6 weeks. | 29 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Disease need | 1 | 1 |
| Overall Study | Incorrect enrolment | 1 | 0 |
| Overall Study | Need GP IIb/IIIa | 1 | 3 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Clopidogrel | Total | Ticagrelor |
|---|---|---|---|
| Age, Continuous | 58.59 years STANDARD_DEVIATION 9.789 | 58.67 years STANDARD_DEVIATION 10.291 | 58.75 years STANDARD_DEVIATION 10.967 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 29 Participants | 57 Participants | 28 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 8 Participants | 10 Participants | 2 Participants |
| Sex: Female, Male Male | 21 Participants | 47 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 12 / 29 | 12 / 31 |
| serious Total, serious adverse events | 1 / 29 | 1 / 31 |
Outcome results
Primary
the Percentage Inhibition of the P2Y12 Receptor
Note: the primary endpoint was changed per the statistical analysis plan prior database lock.
Time frame: at 2 hours after first dose of study drug
Population: FAS (full analysis set). Three randomized patients were excluded from FAS due to any of the following reasons: 1) did not meet exclusion requirments but was randomized, 2)post-treatment blood PRU was not available, 3) pre-treatment blood PRU was missing, and 4) use of prohibited medications.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ticagrelor | the Percentage Inhibition of the P2Y12 Receptor | 48.20 Percentage Inhibition | Standard Deviation 45.41 |
| Clopidogrel | the Percentage Inhibition of the P2Y12 Receptor | 9.78 Percentage Inhibition | Standard Deviation 27.574 |
p-value: 0.0021Wilcoxon (Mann-Whitney)
p-value: 0.000395% CI: [18.559, 58.283]ANOVA
Secondary
the Percentage Inhibition of the P2Y12 Receptor
Time frame: at 0.5 hour after first dose of study drug
Population: PPS (per-protocol set). Seven randomized patients were excluded from PPS due to any of the following reasons: 1) did not meet exclusion requirments but was randomized, 2)post-treatment blood PRU was not available, 3) pre-treatment blood PRU was missing, 4) missing blood PRU at 2h after first dose, and 5) use of prohibited medications.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ticagrelor | the Percentage Inhibition of the P2Y12 Receptor | 8.23 Percentage Inhibition | Standard Deviation 25.81 |
| Clopidogrel | the Percentage Inhibition of the P2Y12 Receptor | -3.91 Percentage Inhibition | Standard Deviation 13.602 |
p-value: 0.0828Wilcoxon (Mann-Whitney)
Secondary
the Percentage Inhibition of the P2Y12 Receptor
Time frame: at 8 hours after first dose of study drug
Population: PPS (per-protocol set). Seven randomized patients were excluded from PPS due to any of the following reasons: 1) did not meet exclusion requirments but was randomized, 2)post-treatment blood PRU was not available, 3) pre-treatment blood PRU was missing, 4) missing blood PRU at 2h after first dose, and 5) use of prohibited medications.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ticagrelor | the Percentage Inhibition of the P2Y12 Receptor | 67.91 Percentage Inhibition | Standard Deviation 34.856 |
| Clopidogrel | the Percentage Inhibition of the P2Y12 Receptor | 25.38 Percentage Inhibition | Standard Deviation 32.738 |
p-value: <0.0001Wilcoxon (Mann-Whitney)
Secondary
the Percentage Inhibition of the P2Y12 Receptor
Time frame: at 24 hours after first dose of study drug
Population: PPS (per-protocol set). Seven randomized patients were excluded from PPS due to any of the following reasons: 1) did not meet exclusion requirments but was randomized, 2)post-treatment blood PRU was not available, 3) pre-treatment blood PRU was missing, 4) missing blood PRU at 2h after first dose, and 5) use of prohibited medications.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ticagrelor | the Percentage Inhibition of the P2Y12 Receptor | 79.25 Percentage Inhibition | Standard Deviation 17.92 |
| Clopidogrel | the Percentage Inhibition of the P2Y12 Receptor | 28.76 Percentage Inhibition | Standard Deviation 26.917 |
p-value: <0.0001Wilcoxon (Mann-Whitney)
Secondary
the Percentage Inhibition of the P2Y12 Receptor
Time frame: at 6 weeks after first dose of study drug
Population: PPS (per-protocol set). Seven randomized patients were excluded from PPS due to any of the following reasons: 1) did not meet exclusion requirments but was randomized, 2)post-treatment blood PRU was not available, 3) pre-treatment blood PRU was missing, 4) missing blood PRU at 2h after first dose, and 5) use of prohibited medications.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ticagrelor | the Percentage Inhibition of the P2Y12 Receptor | 83.78 Percentage Inhibition | Standard Deviation 13.947 |
| Clopidogrel | the Percentage Inhibition of the P2Y12 Receptor | 24.22 Percentage Inhibition | Standard Deviation 33.546 |
p-value: <0.0001Wilcoxon (Mann-Whitney)