A Clinical Trial to Demonstrate the Efficacy of Cangrelor

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 is superior, or at least non-inferior, to that of clopidogrel in subjects requiring PCI.

Official Title
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A Clinical Trial Comparing Cangrelor to Clopidogrel in Subjects Who Require Percutaneous Coronary Intervention (PCI).

Conditions
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Myocardial Infarction (MI), Acute Coronary Syndromes (ACS)

Intervention / Treatment
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* Drug: Cangrelor (P2Y12 inhibitor)
* Drug: clopidogrel (oral P2Y12 inhibitor)
* Drug: Placebo bolus & placebo infusion
* Drug: Placebo capsules - end of infusion
* Drug: Placebo capsules - as soon as possible after randomization


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA To be included in this study, subjects must meet the following 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 or ST-elevation MI. EXCLUSION CRITERIA Subjects will be excluded from the study if they present with any of the following: Not a candidate for PCI Increased bleeding risk: ischemic stroke within the last year or any previous hemorrhagic stroke, tumor, cerebral arteriovenous malformation, or intracranial aneurysm; recent (<1 month) trauma or major surgery (including by-pass 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), or history of thrombocytopenia or neutropenia associated with clopidogrel 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 clopidogrel dose exceeding maintenance dose (ie, >75 mg) at any time in the 5 days preceding randomization Inability to swallow study capsules Glycoprotein IIb/IIIa (GPI) Inhibitor usage within the previous 12 hours [applicable to unstable angina (UA) and non-ST-elevation myocardial infarction (NSTEMI) patients] Subjects excluded for any of the above reasons may be re-screened for participation at any time if the exclusion characteristic has changed.

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>placebo capsules (to match) + 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) + active clopidogrel (600mg) post infusion | Drug: Cangrelor (P2Y12 inhibitor)<br>* IV bolus (30 mcg/kg) & infusion (4 mcg/kg/min) initiated prior to PCI, as soon as possible following randomization (after need for PCI is confirmed) but not more than 30 minutes prior to placement of arterial access. Infusion is to continue 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 (oral P2Y12 inhibitor)<br>* 600 mg active clopidogrel administered as soon as possible following randomization (after need for PCI confirmed), but not more than 30 minutes prior to the placement of the arterial access.<br>* Other names: Plavix;Drug: Placebo capsules - as soon as possible after randomization<br>* Placebo capsules given as soon as possible after randomization to mimic 600mg clopidogrel dosing<br>|
| Active Comparator: Clopidogrel<br>clopidogrel capsules (600 mg) + placebo bolus & infusion (to match) + placebo capsules (to match) post infusion | Drug: clopidogrel (oral P2Y12 inhibitor)<br>* 600 mg active clopidogrel administered as soon as possible following randomization (after need for PCI confirmed), but not more than 30 minutes prior to the placement of the arterial access.<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) | (composite incidence) | randomization through 48 hours after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of All-cause Mortality and MI | (composite incidence) | randomization through 48 hours after randomization | 
| Individual Incidence of All-cause Mortality |  | randomization through 48 hours after randomization | 
| Individual Incidence of IDR |  | randomization through 48 hours after randomization | 
| Incidence of Stroke | Stroke is defined as a sudden, focal neurological defect resulting from a cerebrovascular cause that is not reversible within 24 hours and not due to a readily identifiable cause such as a tumor or trauma. All suspected strokes were reviewed and adjudicated by the Clinical Events Committee (CEC) who considered all clinically relevant information and imaging studies to classify all strokes as: primary hemorrhagic - stroke with focal collections of intracranial blood ischemic cerebral infarction - stroke without focal collections of intracranial blood infarction with hemorrhagic conversion - cerebral infarction with blood thought to represent hemorrhagic conversion and not primary bleeding uncertain - no imaging or autopsy data are available. | randomization through 48 hours after randomization | 
| Incidence of Abrupt Closure, Threatened Abrupt Closure, Need for Urgent Coronary Artery Bypass Graft (CABG) Surgery, or Unsuccessful Procedure During the Index PCI | (a patient could have multiple procedural events) | during index PCI | 
| Incidence of All-cause Mortality, MI or IDR | (composite incidence) | randomization through 30 days after randomization | 
| Incidence of All-cause Mortality or MI | (composite incidence) | randomization through 30 days after randomization | 
| Incidence of All-cause Mortality |  | randomization through 30 days after randomization | 
| Incidence of MI |  | randomization through 30 days after randomization | 
| Incidence of IDR |  | randomization through 30 days after randomization | 
| Incidence of Stroke |  | randomization through 30 days after randomization | 
| Incidence of All Cause Mortality | (excluding STEMI) | randomization through 1 year after randomization | 
| Incidence of GUSTO Severe / Life-threatening Bleeding | Major bleeding (non-CABG-related) - Safety population | randomization through 48 hours after randomization | 
| Incidence of Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding | Major bleeding (non-CABG-related) - Safety population | randomization through 48 hours after randomization | 
| Incidence of ACUITY Major Bleeding | Major bleeding (non-CABG-related) - Safety population | randomization through 48 hours after randomization | 
| Incidence of ACUITY Major Bleeding (Without Hematoma >/= 5 cm) | excludes ACUITY major bleeding for which the only qualifying event was hematoma >/= 5 cm | randomization through 48 hours after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Coronary Syndrome (ACS), Percutaneous Coronary Intervention (PCI), non-ST-segment elevation myocardial infarction (NSTEMI), ST-segment elevation myocardial infarction (STEMI)