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Perioperative Anticoagulant Use for Surgery Evaluation Study (PAUSE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by McMaster University
Sponsor:
Collaborators:
Canadian Institutes of Health Research (CIHR)
Heart and Stroke Foundation of Canada
Information provided by (Responsible Party):
James Douketis, McMaster University
ClinicalTrials.gov Identifier:
NCT02228798
First received: August 25, 2014
Last updated: August 27, 2014
Last verified: August 2014
  Purpose

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 (NOAC) drug, either dabigatran, rivaroxaban or apixaban, and require an elective surgery/procedure.


Condition
Atrial Fibrillation

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Perioperative Anticoagulant Use (Dabigatran, Rivaroxaban, or Apixaban) for Elective Surgery/Procedure Evaluation in Patients With Atrial Fibrillation (AF).

Resource links provided by NLM:


Further study details as provided by McMaster University:

Primary Outcome Measures:
  • Number of Participants with Major Bleeds [ Time Frame: Within 30 days of surgery or procedure ] [ Designated as safety issue: Yes ]

    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.


  • Number of participants with Atrial Thromboembolism [ Time Frame: Within 30 days of surgery or procedure ] [ Designated as safety issue: Yes ]

    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.


Secondary Outcome Measures:
  • Number of participants with Minor bleeding [ Time Frame: 30 days or less after surgery or porcedure ] [ Designated as safety issue: Yes ]
    • 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.

  • Number of participants who die [ Time Frame: 30 days or after surgery or procedure ] [ Designated as safety issue: Yes ]
    Death: death due to any cause.

  • Number of participants that have a Venous Thromboembolism (VTE) [ Time Frame: 30 days or less after surgery ] [ Designated as safety issue: Yes ]
    Venous thromboembolism (VTE): comprising symptomatic deep vein thrombosis and pulmonary embolism, confirmed by objective imaging studies (e.g., ultrasound, CT pulmonary angiogram).

  • Number of participants who acquire Acute Coronary Syndrome [ Time Frame: 30 days or less after surgery or procedure ] [ Designated as safety issue: Yes ]
    • 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.


Other Outcome Measures:
  • Dilute TT test-Laboratory blood test of NOAC levels [ Time Frame: Day of Surgery ] [ Designated as safety issue: No ]
    • NOAC levels will be measured by the dilute TT test expressed in ng/mL.

  • Anti-Xa test for NOAC level [ Time Frame: Day of surgery ] [ Designated as safety issue: No ]
    NOAC levels as measured by an anti-Xa tests, expressed in ng/mL.

  • INR Laboratory Test [ Time Frame: Day of surgery ] [ Designated as safety issue: No ]
    • The INR will be done to compare these tests with novel oral anticoagulant specialized Anti-Xa tests

  • PT Laboratory test [ Time Frame: Day of surgery ] [ Designated as safety issue: No ]
    PT will be measured to compare these tests with novel oral anticoagulant specialized Anti-Xa tests

  • aPTT Laboratory test [ Time Frame: Day of Surgery ] [ Designated as safety issue: No ]
    To compare these tests with novel oral anticoagulant specialized Anti-Xa tests

  • TT Laboratory test [ Time Frame: Day of surgery ] [ Designated as safety issue: No ]
    To compare these tests with novel oral anticoagulant specialized Anti-Xa tests


Biospecimen Retention:   Samples Without DNA

Blood (platelet deprived plasma) will be collected on day of surgery/procedure and measured by 'everyday' coagulation tests that are not NOAC-specific (e.g., activated partial thromboplastin time [aPTT]) and 'specialized' coagulation tests that are NOAC-specific (dilute thrombin time [TT] - HemoclotTM, and anti-factor Xa assays) to determine the effect of the pre-operative NOAC interruption protocol on the level of residual anticoagulation.


Estimated Enrollment: 3291
Study Start Date: July 2014
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Groups/Cohorts
Rivaroxaban
Patients currently taking rivaroxaban that have atrial fibrillation and require surgery or a procedure.
Dabigatran
Patients currently taking dabigatran that have atrial fibrillation and require surgery or a procedure.
Apixaban
Patients currently taking apixaban that have atrial fibrillation and require surgery or a procedure.

Detailed Description:

The primary aim is to demonstrate that a standardized but patient-focused protocol for the perioperative management of each NOAC 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 NOAC interruption protocol on the level of residual anticoagulation, when measured by 'everyday' coagulation tests that are not NOAC-specific (e.g., activated partial thromboplastin time [aPTT]) and 'specialized' coagulation tests that are NOAC-specific (dilute thrombin time [TT] - HemoclotTM, and anti-factor Xa assays).

Approximately 3,300 patients from 15 to 20 centres over a 3 year period will be recruited across Canada for the PAUSE Study.

Patients with Atrial Fibrillation and are currently taking dabigatran, rivaroxaban and apixaban (NOACs) and require elective surgery/procedure will follow a standardized management perioperative protocol for discontinuation of their NOAC prior to surgery. Patients will be discontinuing the NOAC they are currently receiving from 1 to 4 days prior to surgery or procedure, depending on bleed risk, type of NOAC, 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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 NOAC.

Criteria

Inclusion Criteria:

  1. Age 18 years or older
  2. Receiving a NOAC (dabigatran or rivaroxaban or apixaban) for Atrial Fibrillation
  3. Ability to assess patient at lease one day prior to NOAC 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02228798

Contacts
Contact: James Douketis, Md jdouket@mcmaster.ca
Contact: Joanne Duncan, MSc duncanj@mcmaster.ca

Locations
Canada, Alberta
Foothills Hospital Not yet recruiting
Calgary, Alberta, Canada
Contact: Elizabeth MacKay, MD         
Principal Investigator: Elizabeth Mackay, MD         
University of Alberta Active, not recruiting
Edmonton, Alberta, Canada
Canada, British Columbia
Vancouver General Hospital Not yet recruiting
Vancouver, British Columbia, Canada
Contact: Agnes Lee, MD         
Principal Investigator: Agnes Lee, MD         
Victoria Heart Institute Not yet recruiting
Victoria, British Columbia, Canada
Contact: Reginald Smith, MD         
Principal Investigator: Reginald Smith, MD         
Canada, Nova Scotia
QEII Hospital Not yet recruiting
Halifax, Nova Scotia, Canada
Contact: Sudeep Shivakumar, MD         
Principal Investigator: Sudeep Shivakumar, MD         
Canada, Ontario
Hamilton General Hospital Recruiting
Hamilton, Ontario, Canada
Contact: Sam Schulman, MD         
Principal Investigator: Sam Schulman, MD         
Juravinski Hospital Recruiting
Hamilton, Ontario, Canada
Contact: Peter Gross, MD         
Principal Investigator: Peter Gross, MD         
McMaster University Medical Centre Not yet recruiting
Hamilton, Ontario, Canada
Contact: Fred Spencer, MD         
Principal Investigator: Fred Spencer, MD         
St. Joseph's Healthcare Not yet recruiting
Hamilton, Ontario, Canada
Contact: James Douketis, MD         
Principal Investigator: James Douketis, MD         
The Ottawa Hospital Not yet recruiting
Ottawa, Ontario, Canada
Contact: Marc Carrier, MD         
Principal Investigator: Marc Carrier, MD         
North York General Not yet recruiting
Toronto, Ontario, Canada
Contact: Benjamin Bell, MD         
Principal Investigator: Benjamin Bell, MD         
Toronto General Hospital Not yet recruiting
Toronto, Ontario, Canada
Contact: Erik Yeo, MD         
Principal Investigator: Erik Yeo, MD         
University of Manitoba Not yet recruiting
Winnipeg, Ontario, Canada
Contact: Stephen Kowalski, MD         
Principal Investigator: Stephen Kowalski, MD         
Canada, Quebec
Maisonneuve-Rosemont Not yet recruiting
Montreal, Quebec, Canada
Contact: Jeannine Kassis, MD         
Principal Investigator: Jeannine Kassis, MD         
Montreal General Hospital Not yet recruiting
Montreal, Quebec, Canada
Contact: Susan Solymoss, MD         
Principal Investigator: Susan Solymoss, MD         
Montreal Jewish General Hospital Not yet recruiting
Montreal, Quebec, Canada
Contact: Mark Blostein, MD         
Principal Investigator: Mark Blostein, MD         
Sponsors and Collaborators
McMaster University
Canadian Institutes of Health Research (CIHR)
Heart and Stroke Foundation of Canada
Investigators
Principal Investigator: James Douketis, MD McMaster University/St. Joseph's Healthcare
  More Information

No publications provided

Responsible Party: James Douketis, Dr. James Douketis-Principal Investigator, McMaster University
ClinicalTrials.gov Identifier: NCT02228798     History of Changes
Other Study ID Numbers: CIHR-PAUSE-2014, CIHR313156 HSFG-14-0006163
Study First Received: August 25, 2014
Last Updated: August 27, 2014
Health Authority: Canada: Health Canada

Keywords provided by McMaster University:
anticoagulant
atrial fibrillation
surgery
oral anticoagulant
discontinue

Additional relevant MeSH terms:
Atrial Fibrillation
Arrhythmias, Cardiac
Cardiovascular Diseases
Heart Diseases
Pathologic Processes
Anticoagulants
Dabigatran
Rivaroxaban
Antithrombins
Enzyme Inhibitors
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Serine Proteinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014