Acute Coronary Syndrome (ACS)
Conditions
Keywords
Percutaneous Coronary Intervention (PCI), ST elevation myocardial infarction (STEMI), Non-ST elevation myocardial infarction [NSTEMI], Unstable angina (UA), Prasugrel, ACS-PCI
Brief summary
This Phase IV, multicenter trial is designed to assess the efficacy of prasugrel in preventing the formation of blood clots in Taiwanese patients with ACS who have been treated with PCI.
Interventions
DRUGPrasugrel
Prasugrel, oral tablets, containing 3.75 mg per tablet
Sponsors
Daiichi Sankyo Taiwan Ltd., a Daiichi Sankyo Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Is within the age limits and has signed informed consent * Weighs at least 50 kg * Had a previous diagnosis of ACS (UA, STEMI, or NSTEMI), underwent PCI, and received one of the following treatments: * Clopidogrel MD of 75 mg and aspirin 81-100 mg for 2-8 weeks following clopidogrel loading dose (LD) of 300 mg or 600 mg at the time of PCI * Ticagrelor MD of 90 mg twice daily (BID) and aspirin 81-100 mg for 1-4 weeks and switching to clopidogrel MD of 75 mg and aspirin 81-100 mg for 2-4 weeks following ticagrelor LD of 180 mg at the time of PCI * Clopidogrel MD 75 mg and aspirin 81-100 mg for 2-8 weeks following ticagrelor LD of 180 mg at the time of PCI * Or based on investigator's judgment with at least 2 weeks continued use of clopidogrel MD and aspirin 81-100 mg per day before switching to prasugrel and maximum 8 weeks P2Y12 inhibitors MD treatment (prasugrel is not allowed) * Is willing and able to abide by the rules of the research unit and study restrictions * If a woman of child-bearing potential, has a negative serum pregnancy test at screening * Agrees to use at least one method of contraception during the study
Exclusion criteria
* Has active bleeding, significant risk of hemorrhage, or unusual susceptibility to bleed * Had previous hemorrhagic stroke at any time, or transient ischemic attack (TIA) or ischemic stroke within 3 months before the informed consent date * Has known allergies or hypersensitivity to prasugrel, aspirin, or any of their excipients * Has significant hypertension at screening or baseline assessment * Has hemoglobin levels \<10.5 g/dL or hematocrit levels \<30% * Has severe left ventricular systolic dysfunction, ejection fraction \<30% * Is currently undergoing hemodialysis * Has evidence of severe hepatic disease or any of the following: serum alanine transaminase or aspartate transaminase ≥3 times the upper limit of normal (ULN); or bilirubin ≥2 times the ULN at screening * Has any clinical laboratory result performed at screening that is determined to be detrimental to the patient or could compromise the study as determined the Investigator * Has previously participated in this study or in another interventional trial that is not compatible with this study * Has evidence of significant active neuropsychiatric disease, alcohol abuse or drug abuse as determined by the Investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline to Week 4 in P2Y12 Reaction Units During Period 1 | Baseline up to Week 4 post-maintenance dose prasugrel treatment period | The mean change in the P2Y12 reaction unit value assessed from baseline to the end of the 4-week maintenance dose treatment period, after switching from clopidogrel maintenance dose to prasugrel maintenance dose was analyzed with a paired t-test model. Mean changes (including standard deviations) are presented. |
| Number of Participants With Thrombolysis In Myocardial Infarction (TIMI) Major Bleeding Events During Period 2 | End of Week 4 up to Week 28 post-maintenance dose prasugrel treatment period | All safety events were assessed in the overall Safety Population, regardless of the study period. The incidence of major bleeding events (defined as non-coronary artery bypass grafting \[CABG\] thrombolysis in myocardial infarction (TIMI) major) after 28 maintenance dose treatment weeks (optional maximum 12-month P2Y12 inhibitor treatment after ACS participants underwent PCI) are reported. Non-CABG TIMI major bleeding was defined as any intracranial bleeding (excluding microhemorrhages less than 10 millimeter evident only on gradient-echo magnetic resonance imaging); clinically overt signs of hemorrhage associated with a drop in hemoglobin of greater than or equal to 5 g/dL; and fatal bleeding (bleeding that directly results in death within 7 days) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With High On-Treatment Platelet Reactivity (HTPR) During Period 1 | Baseline up to Week 4 post-maintenance dose prasugrel treatment period | High On-Treatment Platelet Reactivity (HTPR) was defined as PRU \>235. |
| Mean Percentage Change From Baseline to Week 4 in Platelet Inhibition During Period 1 | Baseline up to Week 4 post-maintenance dose prasugrel treatment period | The mean percentage change in platelet inhibition at the end of the 4-week maintenance dose prasugrel treatment period, after switching from clopidogrel maintenance dose to prasugrel maintenance dose is reported. |
| Number of Participants With Adverse Events of Special Interest During Period 1 | Baseline up to Week 4 post-maintenance dose prasugrel treatment period | Adverse events of special interest were defined as major and minor bleeding events, clinically relevant bleeding events, and any major adverse cardiovascular events (MACE). Non-CABG TIMI major bleeding was defined as any intracranial bleeding (excluding microhemorrhages less than 10 millimeter evident only on gradient-echo magnetic resonance imaging); clinically overt signs of hemorrhage associated with a drop in hemoglobin of greater than or equal to 5 g/dL; and fatal bleeding (bleeding that directly results in death within 7 days). Non-CABG TIMI minor bleeding was defined as clinically overt (including imaging), resulting in hemoglobin drop of 3 to less than 5 g/dL. |
| Number of Participants With Adverse Events of Special Interest During Period 2 | End of Week 4 up to Week 28 post-maintenance dose prasugrel treatment period | All safety events were assessed in the overall Safety Population, regardless of the study period. Adverse events of special interest were defined as major and minor bleeding events, clinically relevant bleeding events, and any major adverse cardiovascular events (MACE). Non-CABG TIMI major bleeding was defined as any intracranial bleeding (excluding microhemorrhages less than 10 millimeter evident only on gradient-echo magnetic resonance imaging); clinically overt signs of hemorrhage associated with a drop in hemoglobin of greater than or equal to 5 g/dL; and fatal bleeding (bleeding that directly results in death within 7 days). Non-CABG TIMI minor bleeding was defined as clinically overt (including imaging), resulting in hemoglobin drop of 3 to less than 5 g/dL. |
Countries
Taiwan
Participant flow
Recruitment details
A total of 204 participants who met all inclusion criteria and no exclusion criteria were enrolled in the study at 10 clinic sites in Taiwan from 01 Nov 2018 to 19 Aug 2020. One patient did not receive study treatment.
Pre-assignment details
Participants with a previous diagnosis of acute coronary syndrome (ACS) who had undergone percutaneous coronary intervention (PCI) and had been previously treated with a maintenance dose of clopidogrel.
Participants by arm
| Arm | Count |
|---|---|
| Prasugrel Participants with ACS who underwent PCI, and were previously taking clopidogrel, who received a maintenance dose of prasugrel for a total of 28 weeks (optionally up to a maximum 12 months of P2Y12 inhibitor treatment after ACS participants underwent PCI). | 203 |
| Total | 203 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Period 1 | Adverse Event | 1 |
| Period 1 | Did not receive treatment | 1 |
| Period 1 | Withdrawal by Subject | 2 |
| Period 2 | Other | 1 |
| Period 2 | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Prasugrel |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 73 Participants |
| Age, Categorical Between 18 and 65 years | 130 Participants |
| Age, Continuous | 60.6 years STANDARD_DEVIATION 10 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 203 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment Taiwan | 203 participants |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 184 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 203 |
| other Total, other adverse events | 125 / 203 |
| serious Total, serious adverse events | 28 / 203 |
Outcome results
Primary
Mean Change From Baseline to Week 4 in P2Y12 Reaction Units During Period 1
The mean change in the P2Y12 reaction unit value assessed from baseline to the end of the 4-week maintenance dose treatment period, after switching from clopidogrel maintenance dose to prasugrel maintenance dose was analyzed with a paired t-test model. Mean changes (including standard deviations) are presented.
Time frame: Baseline up to Week 4 post-maintenance dose prasugrel treatment period
Population: The P2Y12 reaction unit change from baseline was assessed in patients with available data in the Safety Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prasugrel | Mean Change From Baseline to Week 4 in P2Y12 Reaction Units During Period 1 | -18.2 P2Y12 reaction unit | Standard Deviation 48.1 |
Primary
Number of Participants With Thrombolysis In Myocardial Infarction (TIMI) Major Bleeding Events During Period 2
All safety events were assessed in the overall Safety Population, regardless of the study period. The incidence of major bleeding events (defined as non-coronary artery bypass grafting \[CABG\] thrombolysis in myocardial infarction (TIMI) major) after 28 maintenance dose treatment weeks (optional maximum 12-month P2Y12 inhibitor treatment after ACS participants underwent PCI) are reported. Non-CABG TIMI major bleeding was defined as any intracranial bleeding (excluding microhemorrhages less than 10 millimeter evident only on gradient-echo magnetic resonance imaging); clinically overt signs of hemorrhage associated with a drop in hemoglobin of greater than or equal to 5 g/dL; and fatal bleeding (bleeding that directly results in death within 7 days)
Time frame: End of Week 4 up to Week 28 post-maintenance dose prasugrel treatment period
Population: Number of participants with major bleeding events was assessed in the Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prasugrel | Number of Participants With Thrombolysis In Myocardial Infarction (TIMI) Major Bleeding Events During Period 2 | 4 Participants |
Secondary
Mean Percentage Change From Baseline to Week 4 in Platelet Inhibition During Period 1
The mean percentage change in platelet inhibition at the end of the 4-week maintenance dose prasugrel treatment period, after switching from clopidogrel maintenance dose to prasugrel maintenance dose is reported.
Time frame: Baseline up to Week 4 post-maintenance dose prasugrel treatment period
Population: Platelet inhibition was assessed in participants with available data in the Safety Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prasugrel | Mean Percentage Change From Baseline to Week 4 in Platelet Inhibition During Period 1 | 7.2 percentage of platelet inhibition | Standard Deviation 20.4 |
Secondary
Number of Participants With Adverse Events of Special Interest During Period 1
Adverse events of special interest were defined as major and minor bleeding events, clinically relevant bleeding events, and any major adverse cardiovascular events (MACE). Non-CABG TIMI major bleeding was defined as any intracranial bleeding (excluding microhemorrhages less than 10 millimeter evident only on gradient-echo magnetic resonance imaging); clinically overt signs of hemorrhage associated with a drop in hemoglobin of greater than or equal to 5 g/dL; and fatal bleeding (bleeding that directly results in death within 7 days). Non-CABG TIMI minor bleeding was defined as clinically overt (including imaging), resulting in hemoglobin drop of 3 to less than 5 g/dL.
Time frame: Baseline up to Week 4 post-maintenance dose prasugrel treatment period
Population: Adverse events of special interest were assessed in the Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Prasugrel | Number of Participants With Adverse Events of Special Interest During Period 1 | Any major bleeding adverse events (AE) | 0 Participants |
| Prasugrel | Number of Participants With Adverse Events of Special Interest During Period 1 | Any minor bleeding AE | 1 Participants |
| Prasugrel | Number of Participants With Adverse Events of Special Interest During Period 1 | Any clinically relevant bleeding AE | 2 Participants |
| Prasugrel | Number of Participants With Adverse Events of Special Interest During Period 1 | Any MACE, Cardiovascular death | 0 Participants |
| Prasugrel | Number of Participants With Adverse Events of Special Interest During Period 1 | Any MACE, Non-fatal myocardial infarction | 0 Participants |
| Prasugrel | Number of Participants With Adverse Events of Special Interest During Period 1 | Any MACE, Non-fatal stroke | 0 Participants |
| Prasugrel | Number of Participants With Adverse Events of Special Interest During Period 1 | Any MACE, Stent thrombosis | 0 Participants |
| Prasugrel | Number of Participants With Adverse Events of Special Interest During Period 1 | Any MACE, Revascularization | 0 Participants |
Secondary
Number of Participants With Adverse Events of Special Interest During Period 2
All safety events were assessed in the overall Safety Population, regardless of the study period. Adverse events of special interest were defined as major and minor bleeding events, clinically relevant bleeding events, and any major adverse cardiovascular events (MACE). Non-CABG TIMI major bleeding was defined as any intracranial bleeding (excluding microhemorrhages less than 10 millimeter evident only on gradient-echo magnetic resonance imaging); clinically overt signs of hemorrhage associated with a drop in hemoglobin of greater than or equal to 5 g/dL; and fatal bleeding (bleeding that directly results in death within 7 days). Non-CABG TIMI minor bleeding was defined as clinically overt (including imaging), resulting in hemoglobin drop of 3 to less than 5 g/dL.
Time frame: End of Week 4 up to Week 28 post-maintenance dose prasugrel treatment period
Population: Adverse events of special interest were assessed in the Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Prasugrel | Number of Participants With Adverse Events of Special Interest During Period 2 | Any major bleeding AE | 4 Participants |
| Prasugrel | Number of Participants With Adverse Events of Special Interest During Period 2 | Any minor bleeding AE | 12 Participants |
| Prasugrel | Number of Participants With Adverse Events of Special Interest During Period 2 | Any clinically relevant bleeding AE | 4 Participants |
| Prasugrel | Number of Participants With Adverse Events of Special Interest During Period 2 | Any MACE, Cardiovascular death | 0 Participants |
| Prasugrel | Number of Participants With Adverse Events of Special Interest During Period 2 | Any MACE, Non-fatal myocardial infarction | 2 Participants |
| Prasugrel | Number of Participants With Adverse Events of Special Interest During Period 2 | Any MACE, Non-fatal stroke | 0 Participants |
| Prasugrel | Number of Participants With Adverse Events of Special Interest During Period 2 | Any MACE, Stent thrombosis | 0 Participants |
| Prasugrel | Number of Participants With Adverse Events of Special Interest During Period 2 | Any MACE, Revascularization | 0 Participants |
Secondary
Number of Participants With High On-Treatment Platelet Reactivity (HTPR) During Period 1
High On-Treatment Platelet Reactivity (HTPR) was defined as PRU \>235.
Time frame: Baseline up to Week 4 post-maintenance dose prasugrel treatment period
Population: High On-Treatment Platelet Reactivity was assessed in the Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Prasugrel | Number of Participants With High On-Treatment Platelet Reactivity (HTPR) During Period 1 | Week 4 | 6 Participants |
| Prasugrel | Number of Participants With High On-Treatment Platelet Reactivity (HTPR) During Period 1 | Baseline | 23 Participants |