Clinical trial NCT01675076: Strategy of Continued Versus Interrupted Novel Oral Anti-coagulant at Time of Device Surgery in Patients With Moderate to High Risk of Arterial Thromboembolic Events
Official title: A Randomized Controlled Trial to Investigate Whether a Strategy of Continued Versus Interrupted Novel Oral Anti-coagulant at the Time of Device Surgery, in Patients With Moderate to High Risk of Arterial Thrombo-embolic Events, Leads to a Reduction in the Incidence of Clinically Significant Hematoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hematoma
Keywords: Hematoma
novel oral anti-coagulant (NOAC)
Device surgery
Lead sponsor: Ottawa Heart Institute Research Corporation
Sponsor class: OTHER
Collaborators: name: Boehringer Ingelheim
name: Heart and Stroke Foundation of Canada
name: Bayer
name: Bristol-Myers Squibb
First posted: 2012-08-29
Enrollment: 663
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the best strategy to manage novel oral anti-coagulants (NOACs) at the time of pacemaker or defibrillator surgery. The Investigators hypothesize that performing device surgery without interruption of the novel oral anti-coagulant will result in a reduced rate of clinically significant hematoma.

Detailed description: This is a prospective, open-label, randomized trial, with 1:1 randomization to either continued NOAC or interrupted NOAC in patients with non-rheumatic atrial fibrillation or atrial flutter and at moderate to high risk of arterial thrombo-embolic events who require device surgery.

All patients in the study will be receiving Dabigatran or Rivaroxaban or Apixaban for at least 5 days prior to enrollment. The peri-operative management of the NOAC the patient is receiving is randomized to Interrupted NOAC or Continued NOAC.

Interrupted NOAC arm:

1. Interrupted Dabigatran

   * based on renal function, patients will discontinue Dabigatran 1 day before surgery if GFR \> 50 mL/min, and 2 days before surgery if GFR is 30-50 mL/min.
   * Dabigatran will be resumed at the next regular dose time, \> or = 24 hours after the end of surgery.
2. Interrupted Rivaroxaban

   * patients will discontinue Rivaroxaban 1 full day before surgery.
   * Rivaroxaban will be resumed at the next regular dose time, \> or = 24 hours after the end of surgery.
3. Interrupted Apixaban

   * patients will discontinue Apixaban 1 full day before surgery.
   * Apixaban will be resumed at the next regular dose time, \> or = 24 hours after the end of surgery.

Continued NOAC arm:

-patients will continue their chronic dose of Dabigatran or Rivaroxaban or Apixaban throughout.

All patients will have a baseline clinical lab test of serum creatinine or GRF measured.

Patients will be seen post-op on the day of their surgery for assessment of the surgical site and each day throughout their hospital stay by a blinded member of the research team. A telephone follow-up will be done on day 3-4 post surgery by an unblinded team member. All patients are seen 1-2 weeks post-op at their first routine post-op device clinic visit, for surgical site assessment by the blinded assessor and to complete Quality of Life questionnaires. Patients will be seen for assessment in the case of any bleeding or development of pocket swelling or hematoma. Patients developing a hematoma will be followed until resolution of the hematoma.

Eligibility criteria: Inclusion Criteria:

* any patient undergoing device surgery (ie. de novo device implant or pulse generator change or lead replacement or pocket revision)
* receiving Dabigatran or Rivaroxaban or Apixaban for at least 5 days prior to enrollment
* non-rheumatic atrial fibrillation and/or atrial flutter at moderate or high risk of ATE defined as: i) CHA2DS2VASc score greater than or equal to 2 OR ii) CHA2DS2VASc score \< 2 with plan for cardioversion or defibrillation threshold testing at time of device surgery

Exclusion Criteria:

* unable or unwilling to provide informed consent
* history of noncompliance of medical therapy
* active device infection
* eGFR \< 30 mL/min
* contraindication to NOAC
* rheumatic valvular disease with hemodynamically significant valve lesion
* mechanical heart valve

Primary outcomes:
measure: Clinically significant hematoma
timeFrame: 2 weeks post-op or until resolution of hematoma
Secondary outcomes:
measure: Composite of major peri-operative bleeding events and thrombo-embolic events
timeFrame: 2 weeks post-op
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Foothills Medical Centre
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta-ECAT Group
state: Alberta
city: Victoria
country: Canada
facility: Victoria Cardiac Arrhythmia Trials Inc.
state: British Columbia
city: Hamilton
country: Canada
facility: Hamilton Health Sciences General Campus
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: Toronto
country: Canada
facility: Rouge Valley Health System-Centenary Campus
state: Ontario
city: Toronto
country: Canada
facility: Humber River Hospital
state: Ontario
city: Montreal
country: Canada
facility: Montreal Heart Institute
state: Quebec
city: Montreal
country: Canada
facility: Centre Hospitalier de l'Universite de Montreal (CHUM), Hotel Dieu
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Centre/Montreal General Hospital
state: Quebec
city: Montreal
country: Canada
facility: Hopital Sacre-Coeur
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre Hospitalier Universitaire de Sherbrooke-Hopital Fleurimont
state: Quebec
city: Quebec
country: Canada
facility: Institut Universitaire de Cardiologie et de Pneumologie de Quebec
city: Nahariya
country: Israel
facility: Galilee Medical Center
Study officials:
affiliation: Ottawa Heart Institute Research Corporation
name: David Birnie, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: McGill University
name: Vidal Essebag, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: McMaster University
name: Jeff Healey, MD
role: STUDY_CHAIR
References:
citation: Birnie DH, Healey JS, Wells GA, Ayala-Paredes F, Coutu B, Sumner GL, Becker G, Verma A, Philippon F, Kalfon E, Eikelboom J, Sandhu RK, Nery PB, Lellouche N, Connolly SJ, Sapp J, Essebag V. Continued vs. interrupted direct oral anticoagulants at the time of device surgery, in patients with moderate to high risk of arterial thrombo-embolic events (BRUISE CONTROL-2). Eur Heart J. 2018 Nov 21;39(44):3973-3979. doi: 10.1093/eurheartj/ehy413.
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.