Maintenance of Platelet Inhibition With Cangrelor (Bridge)

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

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 Overview

• Status: Completed
• Conditions: Acute Coronary Syndrome (ACS)
• Intervention / Treatment: Drug: cangrelor; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 221
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037
      • Scripps Clinic / Scripps Green Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cangrelor; 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
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.	Other: Placebo; Placebo IV infusion administered in the same fashion as the active study drug in order to maintain the blind in the study.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The Medicines Company
• Investigators: Principal Investigator: Eric Topol, MD, Scripps

Publications and helpful links

General Publications

• Angiolillo DJ, Firstenberg MS, Price MJ, Tummala PE, Hutyra M, Welsby IJ, Voeltz MD, Chandna H, Ramaiah C, Brtko M, Cannon L, Dyke C, Liu T, Montalescot G, Manoukian SV, Prats J, Topol EJ; BRIDGE Investigators. Bridging antiplatelet therapy with cangrelor in patients undergoing cardiac surgery: a randomized controlled trial. JAMA. 2012 Jan 18;307(3):265-74. doi: 10.1001/jama.2011.2002.

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: October 6, 2008
• First Submitted That Met QC Criteria: October 6, 2008
• First Posted (Estimate): October 7, 2008

Study Record Updates

• Last Update Posted (Estimate): April 4, 2014
• Last Update Submitted That Met QC Criteria: February 21, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Acute Coronary Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Cangrelor
• Other Study ID Numbers: TMC-CAN-08-02