Perioperative Anticoagulant Use for Surgery Evaluation Study Part 2 Pilot

NCT04192552 | Unknown DMC

• 1 other identifier: PAUSE-2-PILOT-2019
• Study Type: interventional
• Target: 201
• Locations: 1 country
• Sites: 3

Brief Summary

The proposed PAUSE-2 RCT study is the logical next step to the Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) study, which was completed on August 31, 2018. Both studies address the perioperative management of patients with atrial fibrillation (AF) who are receiving a direct oral anticoagulant (DOAC) and require an elective surgery/procedure. PAUSE did not address safe management of patients having a high-bleed-risk surgery/neuraxial anesthesia in whom there is concern about bleeding, especially neuraxial-related epidural hematomas that can lead to paralysis; such patients are often managed by the approach recommended by the American Society of Regional Anesthesia (ASRA). In PAUSE-2, investigators will test the hypothesis: (i) for patients having a high-bleed-risk surgery/neuraxial anesthesia, the simpler "PAUSE management" is as safe (non-inferior) to the more complex "ASRA management". PAUSE-2 will establish a standard for perioperative DOAC management in patients having high-bleed-risk surgery or neuraxial anesthesia. To start, this will be a pilot study of a larger PAUSE-2-RCT. The investigators will be conducting this pilot study to assess the feasibility of the study at this smaller scale.

Conditions

Atrial Fibrillation

Keywords

anticoagulant; atrial fibrillation; surgery; oral anticoagulant; high risk; blood thinner; DOAC; interruption; discontinue; elective; perioperative

Outcome Measures

Primary Outcomes (2)

• Number of patients who had a major bleed

  ≥1 of the criteria below: * 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 ≥20 g/L (1.24 mmol/L) or leading to transfusion ≥2 units whole blood or red cells within 48 hours of the bleed * surgical bleed that leads to intervention (e.g., re-operation) or has one of: (i) interferes with mobilization; (ii) leads to delayed wound healing; or (iii) leads to deep wound infection * surgical site bleeding that is unexpected and prolonged and/or sufficiently large to cause hemodynamic instability associated with: (i) drop in hemoglobin ≥20 g/L (1.24 mmol/L); or (ii) transfusion of ≥2 units whole blood or red cells within 48 hours of the bleed

  Each patient will be followed up every 7 days up to completion at 28 days post procedure date

• Number of patients who had an Arterial Thromboembolism (ATE)

  Any of the following: stroke, systemic embolism, and/or transient ischemic attack. * 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 (e.g., CT angiography). * Transient ischemic attack: symptomatic focal neurologic deficit (lasting typically \<1 hour), that occurs with no evidence of acute infarction on CT/MRI of brain.

  Each patient will be followed up every 7 days up to completion at 28 days post procedure date

Secondary Outcomes (5)

• Number of patients who died

  Each patient will be followed up every 7 days up to completion at 28 days post procedure date

• Number of patients who had a Clinically Relevant Non-Major Bleed

  Each patient will be followed up every 7 days up to completion at 28 days post procedure date

• Number of patients who had a Minor Bleed

  Each patient will be followed up every 7 days up to completion at 28 days post procedure date

• Number of patients who had a Venous Thromboembolism (VTE)

  Each patient will be followed up every 7 days up to completion at 28 days post procedure date

• Number of patients who had an Acute Coronary Syndrome

  Each patient will be followed up every 7 days up to completion at 28 days post procedure date

Other Outcomes (3)

• Concentrations of Anti-factor Xa

  Pre-op day 0

• Rate of Diluted Thrombin Time (dTT)

  Pre-op day 0

• Adherence to the DOAC interruption and resumption protocols

  Approximately 1 week pre-op up to completion at 28 days post procedure date

Study Arms (3)

Apixaban

ACTIVE COMPARATOR

Patients currently taking apixaban that have atrial fibrillation and require an elective high-bleed-risk surgery/neuraxial anesthesia.

Other: PAUSE Perioperative DOAC Management; Other: ASRA Perioperative DOAC Management

Dabigatran

ACTIVE COMPARATOR

Patients currently taking dabigatran that have atrial fibrillation and require an elective high-bleed-risk surgery/neuraxial anesthesia.

Other: PAUSE Perioperative DOAC Management; Other: ASRA Perioperative DOAC Management

Rivaroxaban

ACTIVE COMPARATOR

Patients currently taking rivaroxaban that have atrial fibrillation and require an elective high-bleed-risk surgery/neuraxial anesthesia.

Other: PAUSE Perioperative DOAC Management; Other: ASRA Perioperative DOAC Management

Interventions

PAUSE Perioperative DOAC Management OTHER

Apixaban \& Rivaroxaban: Hold DOAC for 2 days before procedure. Re-start DOAC 2+ days post-procedure. Dabigatran (see below): CrCl ≥50: Hold DOAC for 2 days before procedure. Re-start DOAC 2+ days post-procedure. CrCl \<50: Hold DOAC for 4 days before procedure. Re-start DOAC 2+ days post-procedure.

Apixaban; Dabigatran; Rivaroxaban

ASRA Perioperative DOAC Management OTHER

Apixaban \& Rivaroxaban: Hold DOAC for 3 days before procedure. Re-start DOAC 1+ days post-procedure. Dabigatran (see below): CrCl \>80: Hold DOAC for 3 days before procedure. Re-start DOAC 1+ days post-procedure. CrCl 50-80: Hold DOAC for 4 days before procedure. Re-start DOAC 1+ days post-procedure. CrCl 30-49: Hold DOAC for 5 days before procedure. Re-start DOAC 1+ days post-procedure. \*Low-dose heparin bridging can be used if at high A-TE risk

Apixaban; Dabigatran; Rivaroxaban

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult (age ≥18 years) with AF/flutter who is receiving a DOAC: apixaban 2.5 mg or 5 mg BID; dabigatran 110 mg or 150 mg BID; or rivaroxaban 15 mg or 20 mg QD.
• Undergoing an elective surgery/procedure associated with a high-bleed-risk or any surgery/procedure requiring neuraxial anesthesia (includes regional blocks)
• Patient and their clinician are willing to adhere to DOAC interruption/continuation protocols.
• Patient to resume DOAC after surgery/procedure (i.e., no intent to discontinue DOAC).

You may not qualify if:

• Creatinine clearance (CrCl) \<30 mL/min (dabigatran, rivaroxaban) and \<25 mL/min (apixaban) based on the Cockroft-Gault equation, which is recommended for DOAC dosing.
• Patient taking a DOAC that is infrequently used (i.e., edoxaban, \<5% Canadian DOAC market share in 2018) or is not available for clinical use in Canada or Europe (i.e., betrixaban).
• Patient taking a DOAC for a non-AF clinical indication (excluded to maintain study population homogeneity).
• Cognitive impairment or psychiatric illness that precludes collection of follow-up data.
• Inability or unwillingness to provide informed consent.
• Previous participation in PAUSE-2.

Sponsors & Collaborators

• McMaster University: lead
• Hamilton Health Sciences Corporation: collaborator
• St. Joseph's Healthcare Hamilton: collaborator

Study Sites (3)

Hamilton General Hospital

Hamilton, Ontario, Canada

RECRUITING

Juravinski Hospital

Hamilton, Ontario, Canada

NOT YET RECRUITING

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, Canada

NOT YET RECRUITING

MeSH Terms

Conditions

Atrial Fibrillation

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• James D Douketis, MD

  McMaster University/St. Joseph's Healthcare

  PRINCIPAL INVESTIGATOR

Central Study Contacts

James D Douketis, MD

CONTACT

905-522-1155; jdouket@mcmaster.ca

Joanne Duncan, MSc

CONTACT

duncanj@mcmaster.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. James Douketis-Principal Investigator

Model Details: Patients taking apixaban, dabigatran, or rivaroxaban will be randomly assigned to follow 1) PAUSE or 2) ASRA perioperative DOAC management.

Study Record Dates

• First Submitted: November 20, 2019
• First Posted: December 10, 2019
• Study Start: January 9, 2020
• Primary Completion: January 1, 2021
• Study Completion: January 1, 2021
• Last Updated: January 22, 2020

Record last verified: 2020-01

Locations

CA (3)