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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

Phase 3
Completed
Conditions
Hematoma
Interventions
Registration Number
NCT01675076
Lead Sponsor
Ottawa Heart Institute Research Corporation
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
663
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Continued NOACRivaroxaban- Patients continue on their chronic dose of Dabigatran or Rivaroxaban or Apixaban throughout
Continued NOACApixaban- Patients continue on their chronic dose of Dabigatran or Rivaroxaban or Apixaban throughout
Interrupted NOACDabigatranInterrupted 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
Continued NOACDabigatran- Patients continue on their chronic dose of Dabigatran or Rivaroxaban or Apixaban throughout
Interrupted NOACRivaroxabanInterrupted 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
Interrupted NOACApixabanInterrupted 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
Primary Outcome Measures
NameTimeMethod
Clinically significant hematoma2 weeks post-op or until resolution of 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.

Secondary Outcome Measures
NameTimeMethod
Composite of major peri-operative bleeding events and thrombo-embolic events2 weeks post-op

1. Each of the components of the primary outcome

2. Composite of all other major peri-operative bleeding events defined as:

* hemothorax

* cardiac tamponade

* significant pericardial effusion

3. Thrombo-embolic events defined as:

* transient ischemic attack

* stroke

* deep venous thrombosis

* pulmonary embolism

* peripheral embolus to limb

* peripheral embolus to other major organ

4. All cause mortality

5. Cost utilization

6. Patient quality of life and peri-operative pain, and satisfaction

Trial Locations

Locations (15)

Victoria Cardiac Arrhythmia Trials Inc.

🇨🇦

Victoria, British Columbia, Canada

University of Alberta-ECAT Group

🇨🇦

Edmonton, Alberta, Canada

Hamilton Health Sciences General Campus

🇨🇦

Hamilton, Ontario, Canada

Foothills Medical Centre

🇨🇦

Calgary, Alberta, Canada

Southlake Regional Health Centre

🇨🇦

Newmarket, Ontario, Canada

Humber River Hospital

🇨🇦

Toronto, Ontario, Canada

Montreal Heart Institute

🇨🇦

Montreal, Quebec, Canada

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

🇨🇦

Montreal, Quebec, Canada

Hopital Sacre-Coeur

🇨🇦

Montreal, Quebec, Canada

Galilee Medical Center

🇮🇱

Nahariya, Israel

Centre Hospitalier Universitaire de Sherbrooke-Hopital Fleurimont

🇨🇦

Sherbrooke, Quebec, Canada

University of Ottawa Heart Institute

🇨🇦

Ottawa, Ontario, Canada

Rouge Valley Health System-Centenary Campus

🇨🇦

Toronto, Ontario, Canada

McGill University Health Centre/Montreal General Hospital

🇨🇦

Montreal, Quebec, Canada

Institut Universitaire de Cardiologie et de Pneumologie de Quebec

🇨🇦

Quebec, Canada

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