Acute Coronary Syndrome
Conditions
Brief summary
The purpose of this study is to assess the pharmacodynamic effect of ticagrelor in ACS patients undergoing an Ad Hoc PCI
Detailed description
A randomized, open-label, multiple-center, parallel group study to compare the platelet inhibition with VerifyNow assay of ticagrelor versus clopidogrel in troponin negative Acute Coronary Syndrome (ACS) subjects undergoing Ad Hoc percutaneous coronary intervention (PCI)
Interventions
DRUGTicagrelor
180 mg loading dose
DRUGClopidogrel
600 mg loading dose
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
* Provision of signed and dated informed consent before initiation of any study-related procedures * Male or female patients aged 18 years or older * Documented acute coronary syndrome and troponin negative and undergoing Ad Hoc percutaneous coronary intervention (PCI) * Females must be post menopausal or surgically sterile * Taking aspirin as an anti-platelet medication
Exclusion criteria
* Use of any thienopyridine or ticagrelor within 7 days prior to randomization * Any indication for oral anticoagulant (e.g., atrial fibrillation, mitral stenosis or prosthetic heart valve) * Contraindication that ticagrelor or clopidogrel should not be administered Patient requires dialysis * History of intolerance or allergy to aspirin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Inhibition of the P2Y12 Receptor at 2 Hours After Loading Doses of Ticagrelor and Clopidogrel as Measured by P2Y12 Reaction Units (PRU) From VerifyNow™ | 2 hours after the loading dose | Participants with low (\<150) baseline PRU values were excluded. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Inhibition of the P2Y12 Receptor at 0.5 Hours, End of PCI, and 8 Hours After Loading Doses of Ticagrelor and Clopidogrel as Measured by PRU From VerifyNow™ | 0.5 hours, end of PCI, and 8 hours after the loading dose | Participants with low (\<150) baseline PRU values were excluded. |
Countries
United States
Participant flow
Recruitment details
Participants recruited from 15 actively participating sites in the United States of America, from July 2012 until June 2014.
Pre-assignment details
Overall, 343 participants were screened; 102 met inclusion/exclusion criteria, 100 were randomized. 96 participants completed treatment and 97 participants completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Ticagrelor 180 mg loading dose after diagnostic angiography, followed by 90 mg after 12 hours (± 1 hour), with concomitant acetylysalicylic acid (160 mg to 500mg loading dose followed by a daily maintenance dose of 75 mg to 100 mg) | 51 |
| Clopidogrel 600 mg loading dose after diagnostic angiography, with concomitant acetylysalicylic acid (160 mg to 500mg loading dose followed by a daily maintenance dose of 75 mg to 100 mg) | 49 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Failed inclusion criterion after dosed | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Ticagrelor | Clopidogrel | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 15 Participants | 19 Participants | 34 Participants |
| Age, Categorical Between 18 and 65 years | 36 Participants | 30 Participants | 66 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 11 Participants | 11 Participants | 22 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 5 Participants | 1 Participants | 6 Participants |
| Race/Ethnicity, Customized Missing values | 7 Participants | 7 Participants | 8 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 11 Participants | 14 Participants | 25 Participants |
| Race/Ethnicity, Customized Not Reported | 28 Participants | 27 Participants | 55 Participants |
| Race/Ethnicity, Customized White | 33 Participants | 33 Participants | 66 Participants |
| Region of Enrollment United States | 51 Participants | 49 Participants | 100 Participants |
| Sex: Female, Male Female | 17 Participants | 13 Participants | 30 Participants |
| Sex: Female, Male Male | 34 Participants | 36 Participants | 70 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 51 | 1 / 49 |
| serious Total, serious adverse events | 9 / 51 | 5 / 49 |
Outcome results
Primary
Inhibition of the P2Y12 Receptor at 2 Hours After Loading Doses of Ticagrelor and Clopidogrel as Measured by P2Y12 Reaction Units (PRU) From VerifyNow™
Participants with low (\<150) baseline PRU values were excluded.
Time frame: 2 hours after the loading dose
Population: Pharmacodynamic (PD) Analysis Set (N=93; 46 on ticagrelor, 47 on clopidogrel) - included all participants with PD data and without a major protocol deviation thought to significantly affect the PD of ticagrelor or clopidogrel. Participants in the PD Analysis Set with low (\<150) baseline PRU values were excluded from the analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ticagrelor | Inhibition of the P2Y12 Receptor at 2 Hours After Loading Doses of Ticagrelor and Clopidogrel as Measured by P2Y12 Reaction Units (PRU) From VerifyNow™ | 98.4 PRU | Standard Deviation 95.4 |
| Clopidogrel | Inhibition of the P2Y12 Receptor at 2 Hours After Loading Doses of Ticagrelor and Clopidogrel as Measured by P2Y12 Reaction Units (PRU) From VerifyNow™ | 257.5 PRU | Standard Deviation 74.5 |
p-value: <0.00195% CI: [-194.7, -123.5]t-test, 2 sided
Secondary
Inhibition of the P2Y12 Receptor at 0.5 Hours, End of PCI, and 8 Hours After Loading Doses of Ticagrelor and Clopidogrel as Measured by PRU From VerifyNow™
Participants with low (\<150) baseline PRU values were excluded.
Time frame: 0.5 hours, end of PCI, and 8 hours after the loading dose
Population: PD Analysis Set. Participants in the PD Analysis Set with low (\<150) baseline PRU values were excluded from the analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ticagrelor | Inhibition of the P2Y12 Receptor at 0.5 Hours, End of PCI, and 8 Hours After Loading Doses of Ticagrelor and Clopidogrel as Measured by PRU From VerifyNow™ | 0.5 hours | 277.3 PRU | Standard Deviation 73.8 |
| Ticagrelor | Inhibition of the P2Y12 Receptor at 0.5 Hours, End of PCI, and 8 Hours After Loading Doses of Ticagrelor and Clopidogrel as Measured by PRU From VerifyNow™ | 8 hours | 43.8 PRU | Standard Deviation 45.7 |
| Ticagrelor | Inhibition of the P2Y12 Receptor at 0.5 Hours, End of PCI, and 8 Hours After Loading Doses of Ticagrelor and Clopidogrel as Measured by PRU From VerifyNow™ | End of PCI (n=41 for ticagrelor) | 264.2 PRU | Standard Deviation 92.2 |
| Clopidogrel | Inhibition of the P2Y12 Receptor at 0.5 Hours, End of PCI, and 8 Hours After Loading Doses of Ticagrelor and Clopidogrel as Measured by PRU From VerifyNow™ | 0.5 hours | 297.7 PRU | Standard Deviation 69.2 |
| Clopidogrel | Inhibition of the P2Y12 Receptor at 0.5 Hours, End of PCI, and 8 Hours After Loading Doses of Ticagrelor and Clopidogrel as Measured by PRU From VerifyNow™ | 8 hours | 202.3 PRU | Standard Deviation 89.1 |
| Clopidogrel | Inhibition of the P2Y12 Receptor at 0.5 Hours, End of PCI, and 8 Hours After Loading Doses of Ticagrelor and Clopidogrel as Measured by PRU From VerifyNow™ | End of PCI (n=41 for ticagrelor) | 307.8 PRU | Standard Deviation 59.5 |
Comparison: Analysis at 0.5 hours after the loading dosep-value: 0.18295% CI: [-50.5, 9.7]t-test, 2 sided
Comparison: Analysis at 8 hours after the loading dose.p-value: <0.00195% CI: [-189.4, -127.7]t-test, 2 sided
Comparison: Analysis at end of PCI.p-value: 0.0195% CI: [-76.5, -10.7]t-test, 2 sided