Bridge or Continue Coumadin for Device Surgery Randomized Controlled Trial

Official Title: “Bridge or Continue Coumadin for Device Surgery Randomized Controlled Trial (BRUISE CONTROL)”

Many cardiac patients requiring device (defibrillator or pacemaker) related surgery are on chronic oral anticoagulation therapy (usually coumadin). The risk of blood clot formation related to stopping oral anti-coagulant therapy is currently managed by using bridging heparin therapy in patients with moderate to high risk of blood clot formation. There is a substantial risk of bleeding in the pocket where the device is situated (pocket hematoma)related to bridging therapy. The purpose of this study is to compare the current standard of care of bridging with heparin to an experimental strategy of continuing coumadin therapy in higher risk patients undergoing device surgery, with the hypothesis being that the continued oral anti-coagulation group will have a lower pocket hematoma rate as compared to the bridging with heparin group.

Eligible patients will be equally randomized (1:1) to the Conventional/control arm (bridging anti-coagulation)or to the Experimental arm (continued coumadin). In the Conventional arm there are 2 options. Patients with greater than 5 days pre-implant will discontinue oral anti-coagulant (coumadin) 5 days before the procedure,and start full therapeutic doses of subcutaneous low molecular weight heparin (LMWH)3 days before the procedure. Patients with less than 5 days to implant can be given Vitamin K at the investigator's discretion and start full therapeutic doses of either subcutaneous LMWH or IV unfractionated Heparin (choice is at investigator discretion) when the INR is below the therapeutic range for the patient (usually greater than or equal to 2; 2.5 for some valve patients) and surgery to proceed when INR is less than 1.6. Oral anti-coagulant (coumadin) will resume on the evening of the procedure. Full dose LMWH injections or full dose IV heparin will be started 24 hours after surgery.

In the Experimental arm patients will continue on their oral anti-coagulant (coumadin). The INR on the day of surgery will be < 3.0.

ASA will be continued in all patients. Plavix will be continued in patients with drug-eluting stents.

Patients will be monitored for the development of any hematoma or bleeding event during admission. There will be a unblinded team responsible for device implant and follow-up and a blinded team responsible to monitor any bleeding events or hematoma and determine if it meets the primary endpoint criteria for the study. The blinded team will have no knowledge of the treatment arm and will be involved only if the patient develops a hematoma or bleeding event. All hematomas and bleeding events will be followed until resolution.

Intervention(s) in this Clinical Trial

• Drug: low molecular weight heparin or unfractionated heparin
  • For elective patients with greater than 5 days pre-implant; discontinue oral anti-coagulation (coumadin) 5 days before the procedure. Full therapeutic doses of subcutaneous LMWH 3 days before the procedure. Patients with less than 5 days to implant can be given vitamin K (up to 2 mg) at the investigator discretion and start full therapeutic doses of either subcutaneous LMWH or IV Unfractionated Heparin (choice is at investigator's discretion) when INR is below the upper limit of the prescribed therapeutic range for the patient (usually greater than or equal to 2; 2.5 for some valve patients) and surgery to proceed when INR is less than 1.6. Last dose given in the morning(ie. > 24 hours)of the day prior to the procedure. Oral anti-coagulation (coumadin) will be resumed on the evening of the procedure. Full dose LMWH or full dose IV heparin will be restarted 24 hours after surgery.
• Drug: Warfarin or coumadin
  • Continue on oral anti-coagulant (coumadin). INR on the day of surgery will be < 3.0

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: Bridging anti-coagulation
  • Low Molecular Weight Heparin or IV unfractionated Heparin
• Experimental: Continued oral anti-coagulation
  • Coumadin

Primary Measures

• Clinically significant hematoma (defined as hematoma requiring reoperation and/or transfusion and/or unplanned or prolonged hospitalization and/or interruption of LMWH or IV heparin or oral anti-coagulant.
  • Time Frame: Device implant until first routine post-op visit
    Safety Issue?: Yes

Secondary Measures

• Components of the primary outcome,composite of all other major peri-operative bleeding events and thrombo-embolic events.
  • Time Frame: Device implant to first routine post-op visit
    Safety Issue?: Yes

Inclusion Criteria:

• 1. Any patient undergoing elective device surgery (i.e. de novo device implantation or pulse generator change or lead replacement or pocket revision)
• 2. Patient at moderate or high risk of arterial thrombo-embolic events (ATE) or high risk of venous thrombo-embolic events (VTE) (defined as one or more of following):
• Prosthetic mitral valve replacement
• Caged ball or tilting disc aortic valve prosthesis
• Bileaflet aortic valve prosthesis and one or more of: AF (atrial
• Fibrillation/Atrial Flutter), prior stroke or TIA, hypertension, diabetes, CHF age >75
• AFib/Flutter associated with rheumatic valvular heart disease
• Non-rheumatic AFib/Flutter and CHADS2 risk criteria SCORE > 2
• Non-rheumatic AFib/Flutter and stroke or TIA (within 3 months)
• Persistent/permanent AFib/Flutter on day of acceptance for device surgery AND plan for cardioversion or DFT testing at device implant
• Recent (within 3 months) VTE
• Severe thrombophilia (Protein C or S deficiency or anti-thrombin or anti-phospholipid antibodies or multiple abnormalities)
• 3. Willing to self-inject or have a relative or friend or nurse inject LMWH

Exclusion Criteria:

• 1. Unable ro unwilling to provide informed consent
• 2. History of noncompliance of medical therapy
• 3. Renal failure with Cr > 180 umol/l
• 4. Prior Heparin induced thrombocytopenia
• 5. Active device infection

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: University of Ottawa Heart Institute Other

Overall Clinical Trial Officials and Contacts

David Birnie, MD Principal Investigator University of Ottawa Heart Institute  

Overall Contact: Leslie Carlin, RN, BScN 613-798-5555 lcarlin@ottawaheart.ca

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00800137

Study ID Number: UOHI-02

ClinicalTrials.gov Identifier: NCT00800137

Health Authority: Canada: Health Canada