Maintenance of Platelet Inhibition With Cangrelor

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate that patients receiving cangrelor infusion before coronary artery bypass grafting have an acceptable safety profile and can undergo surgery without excessive bleeding peri-operatively.

Official Title
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BRIDGE: Maintenance of Platelet inihiBition With cangRelor After dIscontinuation of ThienopyriDines in Patients Undergoing surGEry

Conditions
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Acute Coronary Syndrome (ACS)

Intervention / Treatment
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* Drug: cangrelor
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent 18 Years of Age Non emergent coronary bypass graft surgery Received a thienopyridine within 48 hours prior to enrollment Exclusion Criteria: Confirmed or suspected pregnancy Cerebrovascular accident within one yar Intracranial neoplasm History of bleeding diathesis Thrombocytopenia

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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 was administered as a continuous IV infusion of 0.75µg/kg/min for a minimum of 48 hours and a maximum of 7 days. | Drug: cangrelor<br> <br> |
| Placebo Comparator: Placebo<br>A placebo infusion was administered as a continuous IV infusion of 0.75µg/kg/min for a minimum of 48 hours and a maximum of 7 days, to maintain the blind. | Other: Placebo<br>* Placebo IV infusion administered in the same fashion as the active study drug in order to maintain the blind in the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stage I: Percentage of Patient Samples That Maintained Platelet Inhibition Levels of Greater Than or Equal to 60% as Reported by the VerifyNow P2Y12 Point of Care Assay. | Endpoint was selected as an approximation of the antiplatelet effect expected to be maintained if oral P2Y12 inhibitors had not been discontinued (60% inhibition of platelets). | During study drug infusion up to 1-6 hours prior to surgery | 
| Stage II: The Percentage of Patients That Maintained Platelet Reaction Units (PRU) < 240, as Determined by the VerifyNow P2Y12 Point of Care Assay, Measured During Study Drug Infusion Pre-surgery. | This endpoint was selected as it is considered by consensus of the Working Group on Platelet Reactivity to be the threshold for the level of platelet inhibition required to maintain a low risk of coronary thrombosis and cardiac ischemic events. Patients had multiple samples and all on-infusion samples had to be <240 PRU to meet the endpoint. | During study drug infusion up to 1-6 hours prior to surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stage II: Analysis of Platelet Reactivity (ITT Population) / Patients With Platelet Reactivity < 240 PRU | This endpoint analyzed the percent of patients with platelet reactivity < 240 PRU at the following timepoints: Baseline - Prior to study drug infusion (washout period from oral P2Y12 inhibition) Last sample during infusion Following discontinuation of study drug infusion | baseline until just prior to surgery (post infusion) | 
| Incidence of Excessive Coronary Artery Bypass Graft (CABG)-Related Bleeding | Defined as the occurrence of surgical re-exploration, 24-hour chest tube output of >1.5 liters (L), and/or packed red blood cell transfusions > 4 units | Randomization through Hospital discharge | 
| Non-CABG (Preoperative) Bleeding - Protocol-defined GUSTO Severe/Life-threatening, Moderate and Mild |  | Randomization until start of CABG surgery | 
| Patients With Blood Product Transfusions up to 7 Days After Surgery or Discharge, Whichever Was Sooner |  | Through 7 days or hospital discharge, whichever was sooner |