Bridge or Continue Coumadin for Device Surgery Randomized Controlled Trial (BRUISECONTROL)

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.

Study Overview

• Status: Terminated
• Conditions: Hematoma
• Intervention / Treatment: Drug: low molecular weight heparin or unfractionated heparin; Drug: Warfarin or coumadin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 984
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • RS
    • Porto Alegre, RS, Brazil, 90620 - 000
      • Instituto de Cardiologia - Fundação Universitária de Cardiologia
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • University of Calgary
    • Edmonton, Alberta, Canada
      • Mazankowski Alberta Heart Institute
  • British Columbia
    • Victoria, British Columbia, Canada, V8R 4R2
      • Royal Jubilee Hospital
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2H 2A6
      • Winnipeg Health Sciences Centre
  • New Brunswick
    • Saint John, New Brunswick, Canada, E2L 4L2
      • St. John Regional Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 3A7
      • QEII Health Sciences Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton Health Science Center
    • Kingston, Ontario, Canada, K7L 2V7
      • Kingston General Hospital
    • Kitchener, Ontario, Canada, N2M 1B2
      • St. Mary's General Hospital
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Center
    • Newmarket, Ontario, Canada, L3Y 2P9
      • Southlake Regional Health Centre
    • Ottawa, Ontario, Canada, K1Y 4W7
      • University of Ottawa Heart Institute
    • Scarborough, Ontario, Canada, M1E 5E9
      • Rouge Valley Hospital
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Mike's Hospital
  • Quebec
    • Laval, Quebec, Canada, H7M 3L9
      • Cité-de-la-Santé Hospital
    • Montreal, Quebec, Canada, H3G 1A4
      • McGill University Health Center
    • Montréal, Quebec, Canada, H2W 1T8
      • Centre Hospitalier de l'Universite de Montreal
    • Montréal, Quebec, Canada, H4J 1C5
      • Hôpital Sacré-Coeur de Montréal
    • Québec, Quebec, Canada, G1V 4G5
      • Hôpital Laval
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Sherbrooke University Hospital Centre CHUS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Bridging anti-coagulation; Low Molecular Weight Heparin or IV unfractionated Heparin	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.
Experimental: Continued oral anti-coagulation; Coumadin	Drug: Warfarin or coumadin; Continue on oral anti-coagulant (coumadin). INR on the day of surgery will be < 3.0

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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.	Device implant until first routine post-op visit

Secondary Outcome Measures

Outcome Measure	Time Frame
Components of the primary outcome,composite of all other major peri-operative bleeding events and thrombo-embolic events.	Device implant to first routine post-op visit

Collaborators and Investigators

• Sponsor: Ottawa Heart Institute Research Corporation
• Collaborators: Canadian Institutes of Health Research (CIHR)

Publications and helpful links

General Publications

• Birnie DH, Healey JS, Wells GA, Verma A, Tang AS, Krahn AD, Simpson CS, Ayala-Paredes F, Coutu B, Leiria TL, Essebag V; BRUISE CONTROL Investigators. Pacemaker or defibrillator surgery without interruption of anticoagulation. N Engl J Med. 2013 May 30;368(22):2084-93. doi: 10.1056/NEJMoa1302946. Epub 2013 May 9.
• Essebag V, Healey JS, Joza J, Nery PB, Kalfon E, Leiria TLL, Verma A, Ayala-Paredes F, Coutu B, Sumner GL, Becker G, Philippon F, Eikelboom J, Sandhu RK, Sapp J, Leather R, Yung D, Thibault B, Simpson CS, Ahmad K, Toal S, Sturmer M, Kavanagh K, Crystal E, Wells GA, Krahn AD, Birnie DH. Effect of Direct Oral Anticoagulants, Warfarin, and Antiplatelet Agents on Risk of Device Pocket Hematoma: Combined Analysis of BRUISE CONTROL 1 and 2. Circ Arrhythm Electrophysiol. 2019 Oct;12(10):e007545. doi: 10.1161/CIRCEP.119.007545. Epub 2019 Oct 15.
• Essebag V, AlTurki A, Proietti R, Healey JS, Wells GA, Verma A, Krahn AD, Simpson CS, Ayala-Paredes F, Coutu B, Leather R, Ahmad K, Toal S, Sapp J, Sturmer M, Kavanagh K, Crystal E, Leiria TLL, Seifer C, Rinne C, Birnie D; BRUISE CONTROL Investigators. Concomitant anti-platelet therapy in warfarin-treated patients undergoing cardiac rhythm device implantation: A secondary analysis of the BRUISE CONTROL trial. Int J Cardiol. 2019 Aug 1;288:87-93. doi: 10.1016/j.ijcard.2019.04.066. Epub 2019 Apr 26.
• Essebag V, Verma A, Healey JS, Krahn AD, Kalfon E, Coutu B, Ayala-Paredes F, Tang AS, Sapp J, Sturmer M, Keren A, Wells GA, Birnie DH; BRUISE CONTROL Investigators. Clinically Significant Pocket Hematoma Increases Long-Term Risk of Device Infection: BRUISE CONTROL INFECTION Study. J Am Coll Cardiol. 2016 Mar 22;67(11):1300-8. doi: 10.1016/j.jacc.2016.01.009.

Helpful Links

• NEJM publication-full study results

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: November 26, 2008
• First Submitted That Met QC Criteria: November 28, 2008
• First Posted (Estimate): December 1, 2008

Study Record Updates

• Last Update Posted (Actual): August 15, 2018
• Last Update Submitted That Met QC Criteria: August 13, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: pocket hematoma; coumadin; device surgery; Pocket hematoma and device surgery
• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage; Hematoma; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin; Calcium heparin; Heparin, Low-Molecular-Weight; Tinzaparin; Dalteparin; Warfarin
• Other Study ID Numbers: UOHI-02