Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition.

Study Overview
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Brief Summary
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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).

Official Title
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A Clinical Trial Comparing Treatment With Cangrelor (in Combination With Usual Care) to Usual Care, in Subjects Who Require Percutaneous Coronary Intervention (PCI).

Conditions
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Atherosclerosis, Acute Coronary Syndrome (ACS)

Intervention / Treatment
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* Drug: Cangrelor
* Drug: clopidogrel
* Drug: Placebo bolus & placebo infusion
* Drug: Placebo capsules - end of PCI
* Drug: Placebo capsules - end of infusion


Participation Criteria
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Eligibility Criteria
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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: Not a candidate for PCI ST-segment elevation myocardial infarction (STEMI) within 48 hours of randomization 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 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 Severe hypertension not adequately controlled by antihypertensive therapy at the time of randomization Receipt of fibrinolytic therapy in the 12 hours preceding randomization Receipt of any thienopyridine (clopidogrel or ticlopidine) in the 7 days preceding randomization Glycoprotein IIb/IIIa (GPI) Inhibitor usage within the previous 12 hours [applicable to unstable angina (UA) and non-ST-elevation myocardial infarction (NSTEMI) patients]

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cangrelor<br>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 | Drug: Cangrelor<br>* 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)<br>Drug: clopidogrel<br>* clopidogrel capsules (600 mg) at end of PCI<br>* Other names: Plavix;Drug: Placebo capsules - end of PCI<br>* Placebo capsules given at the end of PCI to mimic 600mg clopidogrel dosing<br>|
| Active Comparator: Clopidogrel<br>placebo bolus & infusion (to match) + clopidogrel capsules (600 mg) at end of PCI + placebo capsules (to match) immediately post infusion | Drug: clopidogrel<br>* clopidogrel capsules (600 mg) at end of PCI<br>* Other names: Plavix;Drug: Placebo bolus & placebo infusion<br>* 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)<br>Drug: Placebo capsules - end of infusion<br>* Placebo capsules given at the end of infusion to mimic 600mg clopidogrel dosing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of All-cause Mortality, Myocardial Infarction (MI), and Ischemia-driven Revascularization (IDR) | mITT population; (composite incidence) | randomization through 48 hours post randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of All-cause Mortality or MI | mITT population | randomization through 48 hours post randomization | 
| Incidence of All-cause Mortality | mITT population | randomization through 48 hours post randomization | 
| Incidence of MI | mITT population | randomization through 48 hours post randomization | 
| Incidence of IDR | mITT population | randomization through 48 hours post randomization | 
| Incidence of Stent Thrombosis | mITT population | randomization through 48 hours post randomization | 
| Incidence of Stroke | mITT | randomization through 48 hours post randomization | 
| Incidence of All-cause Mortality | mITT population | randomization through 1 year post randomization | 
| 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. | During index PCI | 
| Incidence of GUSTO Severe / Life-threatening | Major bleeding (non-CABG-related) - Safety population | randomization through 48 hours post randomization | 
| Incidence of Thrombolysis in Myocardial Infarction (TIMI) Major | Major bleeding (non-CABG-related) - Safety population | randomization through 48 hours post randomization | 
| Incidence of ACUITY Major Bleeding | Major bleeding (non-CABG-related) - Safety population | randomization through 48 hours post randomization | 
| 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. | randomization through 48 hours post randomization | 
| Incidence of All-cause Mortality, MI, or IDR | mITT population | randomization through 30 days post randomization | 
| Incidence of All-cause Mortality or MI | mITT population | randomization through 30 days post randomization | 
| Incidence of All-cause Mortality | mITT population | randomization through 30 days post randomization | 
| Incidence of MI | mITT population | randomization through 30 days post randomization | 
| Incidence of IDR | mITT population | randomization through 30 days post randomization | 
| Incidence of Stent Thrombosis | mITT population | randomization through 30 days post randomization | 
| Incidence of Stroke | mITT population | randomization through 30 days post randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Percutaneous Coronary Intervention (PCI), ACS