Clinical trial NCT00800137: Bridge or Continue Coumadin for Device Surgery Randomized Controlled Trial
Official title: Bridge or Continue Coumadin for Device Surgery Randomized Controlled Trial (BRUISE CONTROL)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Hematoma
Keywords: coumadin
device surgery
pocket hematoma
Pocket hematoma and device surgery
Lead sponsor: Ottawa Heart Institute Research Corporation
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2008-12-01
Enrollment: 984
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: Device implant until first routine post-op visit
Secondary outcomes:
measure: Components of the primary outcome,composite of all other major peri-operative bleeding events and thrombo-embolic events.
timeFrame: Device implant to first routine post-op visit
Other outcomes:
Locations:
city: Porto Alegre
country: Brazil
facility: Instituto de Cardiologia - Fundação Universitária de Cardiologia
state: RS
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Edmonton
country: Canada
facility: Mazankowski Alberta Heart Institute
state: Alberta
city: Victoria
country: Canada
facility: Royal Jubilee Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: Winnipeg Health Sciences Centre
state: Manitoba
city: Saint John
country: Canada
facility: St. John Regional Hospital
state: New Brunswick
city: Halifax
country: Canada
facility: QEII Health Sciences Centre
state: Nova Scotia
city: Hamilton
country: Canada
facility: Hamilton Health Science Center
state: Ontario
city: Kingston
country: Canada
facility: Kingston General Hospital
state: Ontario
city: Kitchener
country: Canada
facility: St. Mary's General Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences Center
state: Ontario
city: Newmarket
country: Canada
facility: Southlake Regional Health Centre
state: Ontario
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
city: Scarborough
country: Canada
facility: Rouge Valley Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: St. Mike's Hospital
state: Ontario
city: Laval
country: Canada
facility: Cité-de-la-Santé Hospital
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Center
state: Quebec
city: Montréal
country: Canada
facility: Centre Hospitalier de L'Université de Montréal
state: Quebec
city: Montréal
country: Canada
facility: Hôpital Sacré-Coeur de Montréal
state: Quebec
city: Québec
country: Canada
facility: Hôpital Laval
state: Quebec
city: Sherbrooke
country: Canada
facility: Sherbrooke University Hospital Centre CHUS
state: Quebec
Study officials:
affiliation: Ottawa Heart Institute Research Corporation
name: David Birnie, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.