Perioperative Anticoagulant Use for Surgery Evaluation Study

Study Overview
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Brief Summary
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The aim of the Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) Study, is to establish a safe, standardized protocol for the perioperative management of patients with atrial fibrillation (AF) who are receiving a novel oral anticoagulant (DOAC) drug, either dabigatran, rivaroxaban or apixaban, and require an elective surgery/procedure.

Detailed Description
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The primary aim is to demonstrate that a standardized but patient-focused protocol for the perioperative management of each DOAC is safe, with acceptably low rates of perioperative major bleeding (MB) and arterial thromboembolism (ATE). The perioperative protocol is adjusted based on patient renal function and surgery/procedure-related bleed risk, to optimize patient safety, and does not involve heparin bridging anticoagulation. The secondary aim of the PAUSE Study is to determine the effect of the pre-operative DOAC interruption protocol on the level of residual anticoagulation, when measured by 'everyday' coagulation tests that are not DOAC-specific (e.g., activated partial thromboplastin time [aPTT]) and 'specialized' coagulation tests that are DOAC-specific (dilute thrombin time [TT] - HemoclotTM, and anti-factor Xa assays). Approximately 3,300 patients from 15 to 25 centres over a 3.5 year period will be recruited across Canada for the PAUSE Study. Patients with Atrial Fibrillation and are currently taking dabigatran, rivaroxaban and apixaban (DOACs) and require elective surgery/procedure will follow a standardized management perioperative protocol for discontinuation of their DOAC prior to surgery. Patients will be discontinuing the DOAC they are currently receiving from 1 to 4 days prior to surgery or procedure, depending on bleed risk, type of DOAC, and creatinine clearance rate. A blood sample will be taken on the day of the surgery or procedure for measurement of laboratory outcomes (residual level of anticoagulant on day of surgery). Patients will be followed up weekly up to a month for primary outcome assessments.

Official Title
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Perioperative Anticoagulant Use (Dabigatran, Rivaroxaban, or Apixaban) for Elective Surgery/Procedure Evaluation in Patients With Atrial Fibrillation (AF).

Conditions
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Atrial Fibrillation

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older Receiving a DOAC (dabigatran or rivaroxaban or apixaban) for Atrial Fibrillation Ability to assess patient at lease one day prior to DOAC discontinuation Exclusion Criteria: CrCl less than 30 mL per min for dabigatran- and rivaroxaban-treated patients ( less than 25 mL per min for apixaban-treated patients) as estimated by Cockroft-Gault formula Cognitive impairment or psychiatric illness that precludes collection of followup data Inability or unwillingness to provide informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Rivaroxaban<br>Patients currently taking rivaroxaban that have atrial fibrillation and require surgery or a procedure. | |
| Dabigatran<br>Patients currently taking dabigatran that have atrial fibrillation and require surgery or a procedure. | |
| Apixaban<br>Patients currently taking apixaban that have atrial fibrillation and require surgery or a procedure. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Major Bleeds | The first primary outcome is Major Bleed:Bleeding that is fatal or is symptomatic and retroperitoneal, intracranial, intraspinal, intraocular, pericardial, intramuscular with compartment syndrome, or intra-articular. Non-surgical bleeding causing a drop in hemoglobin greater than or equal to 20 g per L or leading to transfusion greater or equal to 2 units of blood within 24 hours.Surgical bleed that leads to intervention or interferes with mobilization or leads to delayed wound healing; or leads to deep wound infection. Surgical site bleeding that is unexpected and prolonged and or sufficiently large to cause hemodynamic instability associated with a drop in hemoglobin greater or equal to 20 g per L or transfusion of greater or equal to 2 units of blood within 24 hours. The second primary outcome is atrial thromboembolism (ATE), comprising: Ischemic stroke,Systemic embolism: symptomatic embolism to upper or lower extremity or abdominal organ or transient ischemic attack. | Within 30 days of surgery or procedure | 
| Number of participants with Atrial Thromboembolism | The second primary outcome is atrial thromboembolism (ATE), comprising: Ischemic stroke: any new focal neurologic deficit that persists for >24 hours or any new focal neurologic deficit of any duration, that occurs with evidence of acute infarction on computed tomography (CT) or magnetic resonance imaging (MRI) of the brain. Systemic embolism: symptomatic embolism to upper or lower extremity or abdominal organ, confirmed intra-operatively or by objective imaging studies (e.g. CT angiography). Transient ischemic attack: symptomatic focal neurologic deficit (lasting typically less than 1 hour), that occurs with no evidence of acute infarction on CT or MRI of brain. | Within 30 days of surgery or procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Minor bleeding | • Minor bleeding: bleeding not satisfying criteria for major bleeding; investigator will report bleeding events using pertinent clinical data and with an assessment from the surgeon. | 30 days or less after surgery or porcedure | 
| Number of participants who die | Death: death due to any cause. | 30 days or after surgery or procedure | 
| Number of participants that have a Venous Thromboembolism (VTE) | Venous thromboembolism (VTE): comprising symptomatic deep vein thrombosis and pulmonary embolism, confirmed by objective imaging studies (e.g., ultrasound, CT pulmonary angiogram). | 30 days or less after surgery | 
| Number of participants who acquire Acute Coronary Syndrome | • Acute coronary syndrome: symptomatic myocardial ischemia, defined by pre-specified clinical and objective EKG- and/or troponin-related criteria N.B. Patients who develop any clinical outcome will be treated according to standards of care. | 30 days or less after surgery or procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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surgery, anticoagulant, atrial fibrillation, oral anticoagulant, discontinue, DOAC, NOAC, blood thinner, interruption