Clinical trial NCT02228798: Perioperative Anticoagulant Use for Surgery Evaluation Study
Official title: Perioperative Anticoagulant Use (Dabigatran, Rivaroxaban, or Apixaban) for Elective Surgery/Procedure Evaluation in Patients With Atrial Fibrillation (AF).
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Atrial Fibrillation
Keywords: anticoagulant
atrial fibrillation
surgery
oral anticoagulant
discontinue
DOAC
NOAC
blood thinner
interruption
Lead sponsor: McMaster University
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: Heart and Stroke Foundation of Canada
First posted: 2014-08-29
Enrollment: 3135
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Those patients who are currently taking dabigatran, rivaroxaban or apixaban for oral anticoagulation used for stroke prevention in atrial fibrillation, and who require its temporary interruption for a surgical or other procedure, will be recruited from 15 to 25 participating sites across Canada.

The study plans to screen 4,114 patients over a 3 year period, with 80 per cent expected enrollment (3,291 patients) from 16 sites across Canada. Equal number of patients, per oral anticoagulant arm will be enrolled, with approximately 1,000 patients taking each DOAC.

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Age 18 years or older
2. Receiving a DOAC (dabigatran or rivaroxaban or apixaban) for Atrial Fibrillation
3. Ability to assess patient at lease one day prior to DOAC discontinuation

Exclusion Criteria:

1. 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
2. Cognitive impairment or psychiatric illness that precludes collection of followup data
3. Inability or unwillingness to provide informed consent

Primary outcomes:
measure: Number of Participants with Major Bleeds
timeFrame: Within 30 days of surgery or procedure
measure: Number of participants with Atrial Thromboembolism
timeFrame: Within 30 days of surgery or procedure
Secondary outcomes:
measure: Number of participants with Minor bleeding
timeFrame: 30 days or less after surgery or porcedure
measure: Number of participants who die
timeFrame: 30 days or after surgery or procedure
measure: Number of participants that have a Venous Thromboembolism (VTE)
timeFrame: 30 days or less after surgery
measure: Number of participants who acquire Acute Coronary Syndrome
timeFrame: 30 days or less after surgery or procedure
Other outcomes:
measure: Dilute TT test-Laboratory blood test of NOAC levels
timeFrame: Day of Surgery
measure: Anti-Xa test for NOAC level
timeFrame: Day of surgery
measure: INR Laboratory Test
timeFrame: Day of surgery
measure: PT Laboratory test
timeFrame: Day of surgery
measure: aPTT Laboratory test
timeFrame: Day of Surgery
measure: TT Laboratory test
timeFrame: Day of surgery
Locations:
city: Aurora
country: United States
facility: Department of Pharmacy, Kaiser Permanente Colorado, Aurora, CO, USA
state: Colorado
city: Evanston
country: United States
facility: NorthShore University HealthSystem
state: Illinois
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Leuven
country: Belgium
facility: Department of Cardiovascular Sciences, University of Leuven
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Halifax
country: Canada
facility: QEII Hospital
state: Nova Scotia
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
city: Hamilton
country: Canada
facility: Juravinski Hospital
state: Ontario
city: Hamilton
country: Canada
facility: McMaster University Medical Centre
state: Ontario
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: North York General
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Winnipeg
country: Canada
facility: University of Manitoba
state: Ontario
city: Montreal
country: Canada
facility: Maisonneuve-Rosemont
state: Quebec
city: Montreal
country: Canada
facility: Montreal General Hospital
state: Quebec
city: Montreal
country: Canada
facility: Montreal Jewish General Hospital
state: Quebec
city: Montreal
country: Canada
facility: St. Mary's Hospital
state: Quebec
city: Larissa
country: Greece
facility: Department of Anesthesiology, University of Thessaly
city: Amsterdam
country: Netherlands
facility: Department of Vascular Medicine, Amsterdam Cardiovascular Sciences
Study officials:
affiliation: McMaster University/St. Joseph's Healthcare
name: James Douketis, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Shaw JR, Li N, Vanassche T, Coppens M, Spyropoulos AC, Syed S, Radwi M, Duncan J, Schulman S, Douketis JD. Predictors of preprocedural direct oral anticoagulant levels in patients having an elective surgery or procedure. Blood Adv. 2020 Aug 11;4(15):3520-3527. doi: 10.1182/bloodadvances.2020002335.