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

NCT01675076 | Completed Phase 3 DMC

• 1 other identifier: UOHI-05
• Study Type: interventional
• Target: 663
• Locations: 2 countries
• Sites: 15

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.

Conditions

Hematoma

Keywords

Hematoma; novel oral anti-coagulant (NOAC); Device surgery

Outcome Measures

Primary Outcomes (1)

• Clinically significant hematoma

  Defined as: 1. Hematoma requiring re-operation \- Defined as a hematoma that continues to expand despite all appropriate non-operative measures, or is producing impending or actual wound breakdown or skin necrosis. Minor hematomas that are evacuated at the time of other re-operation (eg. for lead repositioning) are not considered as a primary outcome. or 2. Hematoma resulting in prolongation of hospitalization \- Defined as extended hospitalization or rehospitalization for \> 24 hours, post index surgery, primarily due to hematoma. or 3. Hematoma requiring interruption of anti-coagulation. - Defined as reversal or intentional withholding of all anticoagulation for \> or = 24 hours, in response to wound hematoma.

  2 weeks post-op or until resolution of hematoma

Secondary Outcomes (1)

• Composite of major peri-operative bleeding events and thrombo-embolic events

  2 weeks post-op

Study Arms (2)

Continued NOAC

EXPERIMENTAL

\- Patients continue on their chronic dose of Dabigatran or Rivaroxaban or Apixaban throughout

Drug: Dabigatran; Drug: Rivaroxaban; Drug: Apixaban

Interrupted NOAC

ACTIVE COMPARATOR

Interrupted Dabigatran: * Discontinue Dabigatran 1 day before surgery if GFR \> 50 mL/min or discontinue 2 days before surgery if GFR 30-50 mL/min * Resume Dabigatran at next regular dose timing \>or = 24 hours after the end of surgery Interrupted Rivaroxaban: * Discontinue Rivaroxaban 1 full day before surgery * Resume Rivaroxaban at next regular dose timing \>or = 24 hours after the end of surgery Interrupted Apixaban: * Discontinue Apixaban 1 full day before surgery * Resume Apixaban at next regular dose timing \>or = 24 hours after the end of surgery

Drug: Dabigatran; Drug: Rivaroxaban; Drug: Apixaban

Interventions

Dabigatran DRUG

NOAC

Also known as: Pradaxa

Continued NOAC; Interrupted NOAC

Rivaroxaban DRUG

NOAC

Also known as: Xarelto

Continued NOAC; Interrupted NOAC

Apixaban DRUG

NOAC

Also known as: Eliquis

Continued NOAC; Interrupted NOAC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ottawa Heart Institute Research Corporation: lead
• Boehringer Ingelheim: collaborator
• Heart and Stroke Foundation of Canada: collaborator
• Bayer: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (15)

Foothills Medical Centre

Calgary, Alberta, T2N 2T9, Canada

Location

University of Alberta-ECAT Group

Edmonton, Alberta, T5H 3V9, Canada

Location

Victoria Cardiac Arrhythmia Trials Inc.

Victoria, British Columbia, V8T 1Z4, Canada

Location

Hamilton Health Sciences General Campus

Hamilton, Ontario, L8L 2X2, Canada

Location

Southlake Regional Health Centre

Newmarket, Ontario, L3Y 2P9, Canada

Location

University of Ottawa Heart Institute

Ottawa, Ontario, K1Y 4W7, Canada

Location

Rouge Valley Health System-Centenary Campus

Toronto, Ontario, M1E 4B9, Canada

Location

Humber River Hospital

Toronto, Ontario, M3M 0B2, Canada

Location

Montreal Heart Institute

Montreal, Quebec, H1T 1C8, Canada

Location

Centre Hospitalier de l'Universite de Montreal (CHUM), Hotel Dieu

Montreal, Quebec, H2W 1T8, Canada

Location

McGill University Health Centre/Montreal General Hospital

Montreal, Quebec, H3G 1A4, Canada

Location

Hopital Sacre-Coeur

Montreal, Quebec, H4J 1C5, Canada

Location

Centre Hospitalier Universitaire de Sherbrooke-Hopital Fleurimont

Sherbrooke, Quebec, JiH 5N4, Canada

Location

Institut Universitaire de Cardiologie et de Pneumologie de Quebec

Québec, G1V 4G5, Canada

Location

Galilee Medical Center

Nahariya, 22100, Israel

Location

Related Publications (2)

• 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.

  PMID: 30462279 RESULT

• 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.

  PMID: 31610718 DERIVED

MeSH Terms

Conditions

Hematoma

Interventions

Dabigatran; Rivaroxaban; apixaban

Condition Hierarchy (Ancestors)

Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines

Study Officials

• David Birnie, MD

  Ottawa Heart Institute Research Corporation

  PRINCIPAL INVESTIGATOR

• Vidal Essebag, MD

  McGill University

  PRINCIPAL INVESTIGATOR

• Jeff Healey, MD

  McMaster University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2012
• First Posted: August 29, 2012
• Study Start: January 1, 2013
• Primary Completion: October 1, 2017
• Study Completion: May 1, 2018
• Last Updated: October 7, 2019

Record last verified: 2019-10

Locations

CA (14); IL (1)