Comparing Angiomax to Heparin With Protamine Reversal in Patients OPCAB (OPCAB)

A Study Comparing Angiomax (Bivalirudin) to Heparin With Protamine Reversal in Patients Undergoing Coronary Artery Bypass (OPCAB) Surgery

The purpose of this study is to examine the safety and efficacy of Angiomax as an alternative anticoagulant to heparin with protamine reversal in patients undergoing off-pump coronary artery bypass graft surgery.

Study Overview

• Status: Completed
• Conditions: Cardiac Surgery; Coronary Artery Bypass Surgery
• Intervention / Treatment: Drug: Bivalirudin; Drug: Heparin; Drug: Protamine

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation

Participation Criteria

Eligibility Criteria

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

Description

Inclusion:

• Provide written informed consent before initiation of any study related procedures.
• Be at least 18 years of age.
• Be accepted for elective off-pump coronary artery bypass graft (CABG) surgery without concomitant cardiac surgical procedures.
• < 4 planned Coronary Artery Bypass Grafts

Exclusion:

• Any prior Cardio-Thoracic Surgical procedures requiring median sternotomy
• Confirmed pregnancy - baseline urine or serum pregnancy test (if woman of childbearing potential).
• Cerebrovascular accident within 6 months before randomization, or any cerebrovascular accident with residual neurological deficit.
• Intracranial neoplasm, arteriovenous malformation, or aneurysm.
• Dependency on renal dialysis or creatinine clearance <30mL/min.
• Ongoing treatment with warfarin (or other oral anticoagulants) at the time of randomization. Patients previously treated with warfarin may be enrolled if warfarin therapy can be safely discontinued and baseline INR is <1.3 times control in the absence of heparin therapy.
• Known allergy to Angiomax or hirudin derived drugs, or known sensitivity to any component of these products.
• Patients receiving clopidogrel within the previous 5 days of randomization.
• Patients receiving a glycoprotein IIb/IIIa inhibitor within 48 hours if abciximab (ReoPro) or within 24 hours if eptifibatide (Integrilin) and tirofiban (Aggrastat) of randomization
• Patients receiving lepirudin or argatroban within the previous 24 hours of randomization.
• Patients receiving low molecular weight heparin (LMWH) or thrombolytics within the previous 12 hours or unfractionated heparin within 30 minutes of randomization.
• Patients with active or prior history of heparin-induced thrombocytopenia (HIT)/heparin-induced thrombocytopenia and thrombosis syndrome (HITTS)*.
• Participation in other clinical research studies involving the evaluation of other investigational drugs or devices within 30 days of randomization.
• Refusal to undergo blood transfusion should it become necessary.
• Any other disease or condition, which, in the judgment of the investigator would place a patient at undue risk by being enrolled in the trial or inability to comply with study requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: bivalirudin; 250mg vial given as 0.75mg/kg intravenous (IV) bolus and 1.75 mg/kg/hr IV infusion for the duration of the procedure with the option to increase or decrease the infusion in 0.25 mg/kg/hr increments or to administer additional 0.1-0.5 mg/kg boluses to maintain an ACT>300 seconds.	Drug: Bivalirudin; 250 mg vial administered as 0.75 mg/kg intravenous (IV) bolus and 1.75 mg/kg/h IV infusion for the duration of surgery with the option to increase or decrease the infusion in 0.25 mg/kg/h increments or to administer additional 0.1-0.5 mg/kg boluses to maintain an activated clotting time (ACT) >300 seconds (s).
Active Comparator: heparin/protamine; 1.5-3.5 mg/kg (200-400 U/kg) intravenous (IV) bolus to target an ACT >300 seconds followed by weight-adjusted boluses as needed during the procedure to achieve/maintain the target ACT. Protamine as needed	Drug: Heparin; : Per institutional practice, at 1.5-3.5 mg/kg (200-400 U/kg) IV bolus to achieve a target ACT of >300 s followed by weight-adjusted boluses as needed during surgery to achieve/maintain the target ACT. Batches from hospital stock.; Drug: Protamine; Per institutional practice. Batches from hospital stock.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Death	Hospital discharge or Day 7
Q-wave MI	hospital discharge or day 7,
Repeat Coronary Revascularization,	hospital discharge or day 7,
Stroke (hemorrhagic or ischemic).	hospital discharge or day 7

Collaborators and Investigators

• Sponsor: The Medicines Company
• Investigators: Study Director: Andrew Sternlicht, MD, The Medicines Company

Study record dates

Study Major Dates

• Study Start: August 1, 2003
• Primary Completion (Actual): May 1, 2004

Study Registration Dates

• First Submitted: November 26, 2003
• First Submitted That Met QC Criteria: November 26, 2003
• First Posted (Estimate): November 27, 2003

Study Record Updates

• Last Update Posted (Estimate): November 10, 2011
• Last Update Submitted That Met QC Criteria: November 8, 2011
• Last Verified: November 1, 2011

More Information

Terms related to this study

• Keywords: CABG; Heparin; OPCAB; Off-Pump Coronary Artery Bypass Graft Surgery; Patients requiring off-pump CABG
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Coagulants; Heparin Antagonists; Heparin; Bivalirudin; Protamines
• Other Study ID Numbers: TMC-BIV-02-07; EVOLUTION