Perioperative Anticoagulant Use for Surgery Evaluation Study

Atrial Fibrillation Clinical Trial

— PAUSE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02228798
• Other study ID #: CIHR-PAUSE-2014
• Secondary ID: CIHR313156 HSFG-
• Status: Completed
• Start date: August 1, 2014
• Est. completion date: August 31, 2018

Study information

• Verified date: June 2019
• Source: McMaster University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3135
• Est. completion date: August 31, 2018
• Est. primary completion date: August 31, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atrial Fibrillation

Locations

Country	Name	City	State
Belgium	Department of Cardiovascular Sciences, University of Leuven	Leuven
Canada	University of Alberta	Edmonton	Alberta
Canada	QEII Hospital	Halifax	Nova Scotia
Canada	Hamilton General Hospital	Hamilton	Ontario
Canada	Juravinski Hospital	Hamilton	Ontario
Canada	McMaster University Medical Centre	Hamilton	Ontario
Canada	St. Joseph's Healthcare	Hamilton	Ontario
Canada	Maisonneuve-Rosemont	Montreal	Quebec
Canada	Montreal General Hospital	Montreal	Quebec
Canada	Montreal Jewish General Hospital	Montreal	Quebec
Canada	St. Mary's Hospital	Montreal	Quebec
Canada	The Ottawa Hospital	Ottawa	Ontario
Canada	North York General	Toronto	Ontario
Canada	Toronto General Hospital	Toronto	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia
Canada	University of Manitoba	Winnipeg	Ontario
Greece	Department of Anesthesiology, University of Thessaly	Larissa
Netherlands	Department of Vascular Medicine, Amsterdam Cardiovascular Sciences	Amsterdam
United States	Department of Pharmacy, Kaiser Permanente Colorado, Aurora, CO, USA	Aurora	Colorado
United States	Henry Ford Health System	Detroit	Michigan
United States	NorthShore University HealthSystem	Evanston	Illinois

Sponsors (3)

Lead Sponsor	Collaborator
McMaster University	Canadian Institutes of Health Research (CIHR), Heart and Stroke Foundation of Canada

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Greece,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Dilute TT test-Laboratory blood test of NOAC levels	• DOAC levels will be measured by the dilute TT test expressed in ng/mL.	Day of Surgery
Other	Anti-Xa test for NOAC level	DOAC levels as measured by an anti-Xa tests, expressed in ng/mL.	Day of surgery
Other	INR Laboratory Test	• The INR will be done to compare these tests with novel oral anticoagulant specialized Anti-Xa tests	Day of surgery
Other	PT Laboratory test	PT will be measured to compare these tests with novel oral anticoagulant specialized Anti-Xa tests	Day of surgery
Other	aPTT Laboratory test	To compare these tests with novel oral anticoagulant specialized Anti-Xa tests	Day of Surgery
Other	TT Laboratory test	To compare these tests with novel oral anticoagulant specialized Anti-Xa tests	Day of surgery
Primary	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
Primary	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	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
Secondary	Number of participants who die	Death: death due to any cause.	30 days or after surgery or procedure
Secondary	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
Secondary	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