Maintenance of Platelet Inhibition With Cangrelor (Bridge)
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||BRIDGE: Maintenance of Platelet inihiBition With cangRelor After dIscontinuation of ThienopyriDines in Patients Undergoing surGEry|
- 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. [ Time Frame: During study drug infusion up to 1-6 hours prior to surgery ] [ Designated as safety issue: No ]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).
- 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. [ Time Frame: During study drug infusion up to 1-6 hours prior to surgery ] [ Designated as safety issue: No ]
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.
- Stage II: Analysis of Platelet Reactivity (ITT Population) / Patients With Platelet Reactivity < 240 PRU [ Time Frame: baseline until just prior to surgery (post infusion) ] [ Designated as safety issue: No ]
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
- Incidence of Excessive Coronary Artery Bypass Graft (CABG)-Related Bleeding [ Time Frame: Randomization through Hospital discharge ] [ Designated as safety issue: Yes ]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
- Non-CABG (Preoperative) Bleeding - Protocol-defined GUSTO Severe/Life-threatening, Moderate and Mild [ Time Frame: Randomization until start of CABG surgery ] [ Designated as safety issue: Yes ]
- Patients With Blood Product Transfusions up to 7 Days After Surgery or Discharge, Whichever Was Sooner [ Time Frame: Through 7 days or hospital discharge, whichever was sooner ] [ Designated as safety issue: Yes ]
|Study Start Date:||October 2008|
|Study Completion Date:||July 2011|
|Primary Completion Date:||June 2011 (Final data collection date for primary outcome measure)|
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.
Placebo Comparator: Placebo
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.
Placebo IV infusion administered in the same fashion as the active study drug in order to maintain the blind in the study.
|United States, California|
|Scripps Clinic / Scripps Green Hospital|
|La Jolla, California, United States, 92037|
|Principal Investigator:||Eric Topol, MD||Scripps|