Acute Coronary Syndrome, Percutaneous Coronary Intervention
Conditions
Keywords
acute coronary syndrome, coronary disease, coronary artery disease
Brief summary
The purpose of the study is to assess the efficacy (prevention of vascular events) and safety (especially bleedings) of Ticagrelor (AZD6140) compared with Clopidogrel, both given on top of low dose aspirin, in Asian/Japanese patients with acute coronary syndrome and a planned percutaneous coronary intervention (PCI).
Interventions
DRUGTicagrelor
90 mg, oral dose twice daily
DRUGClopidogrel
75 mg, oral dose once daily
Low Dose ASA
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provision of signed informed consent * Index event of non-ST or ST segment elevation ACS
Exclusion criteria
* Index event is an acute complication of percutaneous coronary intervention * Patient has undergone Percutaneous Coronary Intervention (PCI) after the index event before the first dose of study treatment * Oral anticoagulation therapy that cannot be stopped * The conditions associated with increased risk of bradycardiac events
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major Bleeding | Ongoing up to12 months | Time to first occurrence of any major bleeding event (adjudicated by an independent Clinical Endpoint Committee (ICEC)). 1-year event rate (%) estimated via Kaplan-Meier method. |
| Major Adverse Cardiac Events (MACE) | Ongoing up to 12 months | Time to first occurrence of any event from the composite of death from vascular causes, Myocardial Infarction (MI) and stroke (adjudicated by an ICEC). 1-year event rate (%) estimated via Kaplan-Meier method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Major and Minor Bleeding | Ongoing up to12 months | Time to first occurrence of any major or minor bleeding event (adjudicated by an independent Clinical Endpoint Committee (ICEC)). 1-year event rate (%) estimated via Kaplan-Meier method. |
| Composite of All-cause Mortality, MI or Stroke | Ongoing up to 12 months | Time to first occurrence of any event from the composite of death from any causes, Myocardial Infarction (MI) and stroke (adjudicated by an ICEC). 1-year event rate (%) estimated via Kaplan-Meier method. |
Countries
Japan, South Korea, Taiwan
Participant flow
Recruitment details
In total, 817 patients were enrolled from 3 countries (Japan, South Korea and Taiwan). Of the randomised patients, most patients were Japanese (723 \[90.3%\]). The first patient was enrolled on 28 February 2010 and the last patient completed the study on 31 July 2012.
Pre-assignment details
In total, 801 patients (401 in the ticagrelor \[AZD6140 90 mg bd\] group and 400 patients in the clopidogrel \[clopidogrel 75 mg od\] group) were randomised to treatment. The reasons for not being randomised were Incorrect enrolment before randomisation and Patient decision (withdrawal of consent).
Participants by arm
| Arm | Count |
|---|---|
| Ticagrelor (AZD6140) Ticagrelor (AZD6140) 90 mg bid | 400 |
| Clopidogrel Clopidogrel 75mg od | 400 |
| Total | 800 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Withdrawal by Subject | 65 | 63 |
Baseline characteristics
| Characteristic | Ticagrelor (AZD6140) | Clopidogrel | Total |
|---|---|---|---|
| Age, Continuous | 67 Years STANDARD_DEVIATION 12 | 66 Years STANDARD_DEVIATION 11 | 67 Years STANDARD_DEVIATION 11 |
| Race/Ethnicity, Customized Chinese | 16 Participants | 19 Participants | 35 Participants |
| Race/Ethnicity, Customized Japanese | 361 Participants | 360 Participants | 721 Participants |
| Race/Ethnicity, Customized Korean | 23 Participants | 21 Participants | 44 Participants |
| Sex: Female, Male Female | 95 Participants | 93 Participants | 188 Participants |
| Sex: Female, Male Male | 305 Participants | 307 Participants | 612 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 327 / 387 | 337 / 380 |
| serious Total, serious adverse events | 92 / 387 | 112 / 380 |
Outcome results
Primary
Major Adverse Cardiac Events (MACE)
Time to first occurrence of any event from the composite of death from vascular causes, Myocardial Infarction (MI) and stroke (adjudicated by an ICEC). 1-year event rate (%) estimated via Kaplan-Meier method.
Time frame: Ongoing up to 12 months
Population: Full Analysis set which includes all randomized patients with available post-randomization efficacy data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ticagrelor (AZD6140) | Major Adverse Cardiac Events (MACE) | 10.2 Percent probability |
| Clopidogrel | Major Adverse Cardiac Events (MACE) | 8.1 Percent probability |
Comparison: No formal statistical comparison based on hypothesis test.95% CI: [0.88, 2.44]Regression, Cox
Primary
Major Bleeding
Time to first occurrence of any major bleeding event (adjudicated by an independent Clinical Endpoint Committee (ICEC)). 1-year event rate (%) estimated via Kaplan-Meier method.
Time frame: Ongoing up to12 months
Population: Safety analysis set which includes all patients who received randomized treatment with available post-treatment safety data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ticagrelor (AZD6140) | Major Bleeding | 11.2 Percent probability |
| Clopidogrel | Major Bleeding | 8.4 Percent probability |
Comparison: No formal statistical comparison.95% CI: [0.94, 2.53]Regression, Cox
Secondary
Composite of All-cause Mortality, MI or Stroke
Time to first occurrence of any event from the composite of death from any causes, Myocardial Infarction (MI) and stroke (adjudicated by an ICEC). 1-year event rate (%) estimated via Kaplan-Meier method.
Time frame: Ongoing up to 12 months
Population: Full Analysis set which includes all randomized patients with available post-randomization efficacy data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ticagrelor (AZD6140) | Composite of All-cause Mortality, MI or Stroke | 10.5 Percent probability |
| Clopidogrel | Composite of All-cause Mortality, MI or Stroke | 8.1 Percent probability |
Comparison: No formal statistical comparison based on hypothesis test.95% CI: [0.91, 2.5]Regression, Cox
Secondary
Major and Minor Bleeding
Time to first occurrence of any major or minor bleeding event (adjudicated by an independent Clinical Endpoint Committee (ICEC)). 1-year event rate (%) estimated via Kaplan-Meier method.
Time frame: Ongoing up to12 months
Population: Safety analysis set which includes all patients who received randomized treatment with available post-treatment safety data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ticagrelor (AZD6140) | Major and Minor Bleeding | 26.8 Percent probability |
| Clopidogrel | Major and Minor Bleeding | 16.2 Percent probability |
Comparison: No formal statistical comparison.95% CI: [1.23, 2.4]Regression, Cox