Acute Coronary Syndrome (ACS), Atherosclerosis
Conditions
Keywords
Percutaneous Coronary Intervention (PCI), ACS
Brief summary
The primary objective of this study is to demonstrate that the efficacy of cangrelor (combined with usual care) is superior to that of usual care, in subjects requiring percutaneous coronary intervention (PCI) as measured by a composite of all-cause mortality, myocardial infarction (MI), and ischemia-driven revascularization (IDR).
Interventions
DRUGCangrelor
cangrelor bolus (30 mcg/kg) & cangrelor infusion (4 mcg/kg/min) administered from randomization for at least 2 hours, or until the end of the PCI, whichever is longer with the option to extend up to 4 hours maximum (per investigator discretion)
DRUGclopidogrel
clopidogrel capsules (600 mg) at end of PCI
placebo bolus (30 mcg/kg) & placebo infusion (4 mcg/kg/min) administered from randomization for at least 2 hours, or until the end of the PCI, whichever is longer with the option to extend up to 4 hours maximum (per investigator discretion)
DRUGPlacebo capsules - end of PCI
Placebo capsules given at the end of PCI to mimic 600mg clopidogrel dosing
Placebo capsules given at the end of infusion to mimic 600mg clopidogrel dosing
Sponsors
The Medicines Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Angiography demonstrating atherosclerosis amenable to treatment by percutaneous coronary intervention (PCI) with or without stent implantation and diagnosis of Acute Coronary Syndrome (ACS) by elevated cardiac markers or ischemic chest discomfort w/electrocardiogram changes + age \> 65 or diabetes.
Exclusion criteria
1. Not a candidate for PCI 2. ST-segment elevation myocardial infarction (STEMI) within 48 hours of randomization 3. Increased bleeding risk: ischemic stroke within the last year or any previous hemorrhagic stroke, intra-cranial tumor, cerebral arteriovenous malformation, or intracranial aneurysm; recent (\<1 month) trauma or major surgery \[including coronary artery bypass graft (CABG) surgery\]; currently receiving warfarin, active bleeding 4. Impaired hemostasis: known International Normalized Ratio (INR) \>1.5 at screening; past or present bleeding disorder (including congenital bleeding disorders such as von Willebrand's disease or hemophilia, acquired bleeding disorders, and unexplained clinically significant bleeding disorders), thrombocytopenia (platelet count \<100,000/µL) at screening 5. Severe hypertension not adequately controlled by antihypertensive therapy at the time of randomization 6. Receipt of fibrinolytic therapy in the 12 hours preceding randomization 7. Receipt of any thienopyridine (clopidogrel or ticlopidine) in the 7 days preceding randomization 8. Glycoprotein IIb/IIIa (GPI) Inhibitor usage within the previous 12 hours \[applicable to unstable angina (UA) and non-ST-elevation myocardial infarction (NSTEMI) patients\]
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of All-cause Mortality, Myocardial Infarction (MI), and Ischemia-driven Revascularization (IDR) | randomization through 48 hours post randomization | mITT population; (composite incidence) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of All-cause Mortality | randomization through 48 hours post randomization | mITT population |
| Incidence of MI | randomization through 48 hours post randomization | mITT population |
| Incidence of IDR | randomization through 48 hours post randomization | mITT population |
| Incidence of Stent Thrombosis | randomization through 48 hours post randomization | mITT population |
| Incidence of Stroke | randomization through 48 hours post randomization | mITT |
| Incidence of All-cause Mortality or MI | randomization through 48 hours post randomization | mITT population |
| Incidence of GUSTO Severe / Life-threatening | randomization through 48 hours post randomization | Major bleeding (non-CABG-related) - Safety population |
| Incidence of Thrombolysis in Myocardial Infarction (TIMI) Major | randomization through 48 hours post randomization | Major bleeding (non-CABG-related) - Safety population |
| Incidence of ACUITY Major Bleeding | randomization through 48 hours post randomization | Major bleeding (non-CABG-related) - Safety population |
| Incidence of ACUITY Major Bleeding Without Hematoma >/= 5 cm | randomization through 48 hours post randomization | Major bleeding (non-CABG-related) - Safety population excludes ACUITY major bleeding for which the only qualifying event was hematoma \>/= 5 cm. |
| Incidence of All-cause Mortality, MI, or IDR | randomization through 30 days post randomization | mITT population |
| Incidence of Procedure Events [Abrupt Closure, Threatened Abrupt Closure, Need for Urgent Coronary Artery Bypass Graft (CABG) Surgery, Unsuccessful Procedure, New Thrombus or Suspected Thrombus, and/or Acute Stent Thrombosis] | During index PCI | mITT population A patient could have multiple procedural events. |
Countries
United States
Participant flow
Recruitment details
Patients were selected for randomization based on the need for percutaneous coronary intervention (PCI). Randomization could only occur after the need for PCI was confirm by angiography.
Participants by arm
| Arm | Count |
|---|---|
| Cangrelor cangrelor bolus (30 mcg/kg) & infusion (4 mcg/kg/min) administered from randomization for at least 2 hours, or until the end of the PCI, whichever is longer with the option to extend up to 4 hours maximum (per investigator discretion) + placebo capsules (to match) at end of PCI + active clopidogrel (600mg) immediately post infusion | 2,656 |
| Clopidogrel placebo bolus & infusion (to match) + clopidogrel capsules (600 mg) at end of PCI + placebo capsules (to match) immediately post infusion | 2,645 |
| Total | 5,301 |
Baseline characteristics
| Characteristic | Cangrelor | Clopidogrel | Total |
|---|---|---|---|
| Age, Continuous | 62.5 years STANDARD_DEVIATION 11.4 | 62.5 years STANDARD_DEVIATION 11.3 | 62.5 years STANDARD_DEVIATION 11.4 |
| Region of Enrollment Argentina | 39 participants | 42 participants | 81 participants |
| Region of Enrollment Belarus | 33 participants | 31 participants | 64 participants |
| Region of Enrollment Brazil | 48 participants | 49 participants | 97 participants |
| Region of Enrollment Bulgaria | 403 participants | 394 participants | 797 participants |
| Region of Enrollment Canada | 3 participants | 2 participants | 5 participants |
| Region of Enrollment Czech Republic | 342 participants | 345 participants | 687 participants |
| Region of Enrollment Georgia | 47 participants | 43 participants | 90 participants |
| Region of Enrollment India | 235 participants | 236 participants | 471 participants |
| Region of Enrollment Korea, Republic of | 159 participants | 166 participants | 325 participants |
| Region of Enrollment Lithuania | 54 participants | 55 participants | 109 participants |
| Region of Enrollment Netherlands | 31 participants | 29 participants | 60 participants |
| Region of Enrollment New Zealand | 22 participants | 20 participants | 42 participants |
| Region of Enrollment Russian Federation | 215 participants | 218 participants | 433 participants |
| Region of Enrollment Slovakia | 33 participants | 27 participants | 60 participants |
| Region of Enrollment South Africa | 102 participants | 100 participants | 202 participants |
| Region of Enrollment Spain | 17 participants | 21 participants | 38 participants |
| Region of Enrollment Thailand | 58 participants | 58 participants | 116 participants |
| Region of Enrollment United States | 815 participants | 809 participants | 1624 participants |
| Sex: Female, Male Female | 747 Participants | 782 Participants | 1529 Participants |
| Sex: Female, Male Male | 1909 Participants | 1863 Participants | 3772 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 596 / 2,662 | 530 / 2,650 |
| serious Total, serious adverse events | 48 / 2,662 | 55 / 2,650 |
Outcome results
Primary
Incidence of All-cause Mortality, Myocardial Infarction (MI), and Ischemia-driven Revascularization (IDR)
mITT population; (composite incidence)
Time frame: randomization through 48 hours post randomization
Population: mITT population, based on available data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cangrelor | Incidence of All-cause Mortality, Myocardial Infarction (MI), and Ischemia-driven Revascularization (IDR) | 185 participants |
| Clopidogrel | Incidence of All-cause Mortality, Myocardial Infarction (MI), and Ischemia-driven Revascularization (IDR) | 210 participants |
Secondary
Incidence of ACUITY Major Bleeding
Major bleeding (non-CABG-related) - Safety population
Time frame: randomization through 48 hours post randomization
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cangrelor | Incidence of ACUITY Major Bleeding | 145 participants |
| Clopidogrel | Incidence of ACUITY Major Bleeding | 91 participants |
Secondary
Incidence of ACUITY Major Bleeding Without Hematoma >/= 5 cm
Major bleeding (non-CABG-related) - Safety population excludes ACUITY major bleeding for which the only qualifying event was hematoma \>/= 5 cm.
Time frame: randomization through 48 hours post randomization
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cangrelor | Incidence of ACUITY Major Bleeding Without Hematoma >/= 5 cm | 43 participants |
| Clopidogrel | Incidence of ACUITY Major Bleeding Without Hematoma >/= 5 cm | 29 participants |
Secondary
Incidence of All-cause Mortality
mITT population
Time frame: randomization through 1 year post randomization
Population: mITT population, based on available data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cangrelor | Incidence of All-cause Mortality | 94 participants |
| Clopidogrel | Incidence of All-cause Mortality | 113 participants |
Secondary
Incidence of All-cause Mortality
mITT population
Time frame: randomization through 30 days post randomization
Population: mITT population, based on available data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cangrelor | Incidence of All-cause Mortality | 35 participants |
| Clopidogrel | Incidence of All-cause Mortality | 45 participants |
Secondary
Incidence of All-cause Mortality
mITT population
Time frame: randomization through 48 hours post randomization
Population: mITT population, based on available data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cangrelor | Incidence of All-cause Mortality | 6 participants |
| Clopidogrel | Incidence of All-cause Mortality | 18 participants |
Secondary
Incidence of All-cause Mortality, MI, or IDR
mITT population
Time frame: randomization through 30 days post randomization
Population: mITT population, based on available data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cangrelor | Incidence of All-cause Mortality, MI, or IDR | 227 participants |
| Clopidogrel | Incidence of All-cause Mortality, MI, or IDR | 249 participants |
Secondary
Incidence of All-cause Mortality or MI
mITT population
Time frame: randomization through 30 days post randomization
Population: mITT population, based on available data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cangrelor | Incidence of All-cause Mortality or MI | 213 participants |
| Clopidogrel | Incidence of All-cause Mortality or MI | 233 participants |
Secondary
Incidence of All-cause Mortality or MI
mITT population
Time frame: randomization through 48 hours post randomization
Population: mITT population, based on available data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cangrelor | Incidence of All-cause Mortality or MI | 180 participants |
| Clopidogrel | Incidence of All-cause Mortality or MI | 204 participants |
Secondary
Incidence of GUSTO Severe / Life-threatening
Major bleeding (non-CABG-related) - Safety population
Time frame: randomization through 48 hours post randomization
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cangrelor | Incidence of GUSTO Severe / Life-threatening | 9 participants |
| Clopidogrel | Incidence of GUSTO Severe / Life-threatening | 6 participants |
Secondary
Incidence of IDR
mITT population
Time frame: randomization through 30 days post randomization
Population: mITT population, based on available data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cangrelor | Incidence of IDR | 37 participants |
| Clopidogrel | Incidence of IDR | 46 participants |
Secondary
Incidence of IDR
mITT population
Time frame: randomization through 48 hours post randomization
Population: mITT population, based on available data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cangrelor | Incidence of IDR | 19 participants |
| Clopidogrel | Incidence of IDR | 24 participants |
Secondary
Incidence of MI
mITT population
Time frame: randomization through 48 hours post randomization
Population: mITT population, based on available data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cangrelor | Incidence of MI | 177 participants |
| Clopidogrel | Incidence of MI | 191 participants |
Secondary
Incidence of MI
mITT population
Time frame: randomization through 30 days post randomization
Population: mITT population, based on available data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cangrelor | Incidence of MI | 189 participants |
| Clopidogrel | Incidence of MI | 201 participants |
Secondary
Incidence of Procedure Events [Abrupt Closure, Threatened Abrupt Closure, Need for Urgent Coronary Artery Bypass Graft (CABG) Surgery, Unsuccessful Procedure, New Thrombus or Suspected Thrombus, and/or Acute Stent Thrombosis]
mITT population A patient could have multiple procedural events.
Time frame: During index PCI
Population: mITT population, based on available data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cangrelor | Incidence of Procedure Events [Abrupt Closure, Threatened Abrupt Closure, Need for Urgent Coronary Artery Bypass Graft (CABG) Surgery, Unsuccessful Procedure, New Thrombus or Suspected Thrombus, and/or Acute Stent Thrombosis] | 122 participants |
| Clopidogrel | Incidence of Procedure Events [Abrupt Closure, Threatened Abrupt Closure, Need for Urgent Coronary Artery Bypass Graft (CABG) Surgery, Unsuccessful Procedure, New Thrombus or Suspected Thrombus, and/or Acute Stent Thrombosis] | 142 participants |
Secondary
Incidence of Stent Thrombosis
mITT population
Time frame: randomization through 48 hours post randomization
Population: mITT population, based on available data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cangrelor | Incidence of Stent Thrombosis | 5 participants |
| Clopidogrel | Incidence of Stent Thrombosis | 16 participants |
Secondary
Incidence of Stent Thrombosis
mITT population
Time frame: randomization through 30 days post randomization
Population: mITT population, based on available data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cangrelor | Incidence of Stent Thrombosis | 15 participants |
| Clopidogrel | Incidence of Stent Thrombosis | 28 participants |
Secondary
Incidence of Stroke
mITT population
Time frame: randomization through 30 days post randomization
Population: mITT population, based on available data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cangrelor | Incidence of Stroke | 6 participants |
| Clopidogrel | Incidence of Stroke | 5 participants |
Secondary
Incidence of Stroke
mITT
Time frame: randomization through 48 hours post randomization
Population: mITT population, based on available data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cangrelor | Incidence of Stroke | 7 participants |
| Clopidogrel | Incidence of Stroke | 5 participants |
Secondary
Incidence of Thrombolysis in Myocardial Infarction (TIMI) Major
Major bleeding (non-CABG-related) - Safety population
Time frame: randomization through 48 hours post randomization
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cangrelor | Incidence of Thrombolysis in Myocardial Infarction (TIMI) Major | 4 participants |
| Clopidogrel | Incidence of Thrombolysis in Myocardial Infarction (TIMI) Major | 9 participants |