Perioperative Anticoagulant Management for Atrial Fibrillation

(PAUSE 2 RCT Trial)

Recruiting at 13 trial locations

Overseen By James Douketis, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: McMaster University

Must be taking: DOACs

Must not be taking: Low-dose DOACs

Disqualifiers: Unusual site thrombosis, Low CrCL, Cognitive impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

920 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it involves managing anticoagulant medications (blood thinners) for surgery. It's best to discuss with the trial team or your doctor.

What data supports the effectiveness of the drug ASRA Perioperative DOAC Management for atrial fibrillation?

The PAUSE study suggests that the perioperative management protocol for direct oral anticoagulants (DOACs) is safe for patients with atrial fibrillation, with low expected risks for major bleeding and arterial thromboembolism. This protocol is designed to be easily applied in clinical practice, providing a standardized yet patient-specific approach. ^{1 2 3 4 5}

Is the perioperative anticoagulant management for atrial fibrillation generally safe for humans?

The PAUSE study found that the perioperative management of direct oral anticoagulants (DOACs) in patients with atrial fibrillation is generally safe, with low rates of major bleeding and thromboembolic events. The study showed that the standardized management protocol is effective in minimizing risks, with major bleeding rates of 3.02% for apixaban, 2.84% for dabigatran, and 4.16% for rivaroxaban. ^{2 4 6 7 8}

How does the PAUSE perioperative DOAC management differ from other treatments for atrial fibrillation?

The PAUSE perioperative DOAC management is unique because it provides a standardized yet patient-specific protocol for managing direct oral anticoagulants (DOACs) around the time of surgery, considering factors like the type of DOAC, the patient's kidney function, and the bleeding risk of the surgery. This approach aims to safely balance the risk of bleeding and clotting, unlike traditional methods that may not be as tailored to individual patient needs. ^{1 2 4 6 9}

What is the purpose of this trial?

PAUSE 2 study is a prospective, open-label, blinded-endpoint non-inferiority RCT of PAUSE vs. ASRA management in DOAC treated high risk patients with AF/VTE who need elective high bleed risk surgery/procedure and/or any procedure involving neuraxial anesthesia. The purpose of the PAUSE 2 study is to show that PAUSE management will be as safe (i.e., non-inferior) as ASRA management, with 95% of patients having low/undetectable pre-operative DOAC levels \<30 ng/mL in each group., at the time of surgery/neuraxial.

Research Team

James Douketis, MD

Principal Investigator

McMaster University/St. Joseph's Healthcare

Joseph Shaw, MD

Principal Investigator

The Ottawa Hospital

Eligibility Criteria

This trial is for patients with atrial fibrillation or deep vein thrombosis who are on DOACs (Dabigatran, Rivaroxaban, Apixaban, Edoxaban) and need elective surgery or a procedure that has a high risk of bleeding. Specific eligibility criteria were not provided.

Inclusion Criteria

I am an adult with AF/flutter or VTE and need a specific blood thinner dose.

I am a high-risk patient scheduled for surgery with a high risk of bleeding or requiring specific types of anesthesia.

Exclusion Criteria

Cognitive impairment or psychiatric illness that precludes reliable contact during follow up

My kidney function is low, but specific to my medication type.

Unable or unwilling to provide consent

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-operative Management

Participants interrupt DOACs for 2 days before surgery without heparin bridging or DOAC level testing (PAUSE) or follow ASRA guidelines with 72-120 hours DOAC interruption and possible heparin bridging and DOAC level testing.

2-5 days

Surgery/Procedure

Participants undergo elective high bleed risk surgery or neuraxial procedure.

1 day

Post-operative Management

Participants resume DOACs 2 days after surgery without heparin bridging or DOAC level testing (PAUSE) or follow ASRA guidelines with possible heparin bridging and DOAC level testing.

2-5 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments for bleeding and thromboembolic events.

28 days

Treatment Details

Interventions

• ASRA Perioperative DOAC Management
• PAUSE Perioperative DOAC Management

Trial Overview The PAUSE-2 study compares two ways to manage blood thinners before surgery: the PAUSE method versus the ASRA guidelines. It's designed to see if the PAUSE approach is just as safe in ensuring low levels of blood thinners at surgery time.

Participant Groups

Group I: Apixaban Active Control 2 Interventions

Patients currently taking Apixaban that have atrial fibrillation or Venous Thromboembolism and require an elective high bleed risk surgery or neuraxial anesthesia.

Group II: Dabigatran Active Control 2 Interventions

Patients currently taking Dabigatran that have atrial fibrillation or Venous Thromboembolism and require an elective high bleed risk surgery or neuraxial anesthesia.

Group III: Rivaroxaban Active Control 2 Interventions

Patients currently taking Rivaroxaban that have atrial fibrillation or Venous Thromboembolism and require an elective high bleed risk surgery or neuraxial anesthesia.

Group IV: Edoxaban Active Control 2 Interventions

Patients currently taking Edoxaban that have atrial fibrillation or Venous Thromboembolism and require an elective high bleed risk surgery or neuraxial anesthesia.

Who Is Running the Clinical Trial?

McMaster University

Lead Sponsor

Trials

936

Recruited

2,630,000+

References

1. England pubmed.ncbi.nlm.nih.gov

Coagulation assays and direct oral anticoagulant levels among patients having an elective surgery or procedure. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

The Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) Study for Patients on a Direct Oral Anticoagulant Who Need an Elective Surgery or Procedure: Design and Rationale. [2021]

3. Germany pubmed.ncbi.nlm.nih.gov

Management of DOAC in Patients Undergoing Planned Surgery or Invasive Procedure: Italian Federation of Centers for the Diagnosis of Thrombotic Disorders and the Surveillance of the Antithrombotic Therapies (FCSA) Position Paper. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

The perioperative management of new direct oral anticoagulants: a question without answers. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Peri-procedural management of dabigatran and rivaroxaban: Duration of anticoagulant discontinuation and drug concentrations. [2015]

6. England pubmed.ncbi.nlm.nih.gov

Predictors of Bleeding in the Perioperative Anticoagulant Use for Surgery Evaluation Study. [2021]

7. Germany pubmed.ncbi.nlm.nih.gov

Effect of Direct Oral Anticoagulant, Patient, and Surgery Characteristics on Clinical Outcomes in the Perioperative Anticoagulation Use for Surgery Evaluation Study. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Predictors of preprocedural direct oral anticoagulant levels in patients having an elective surgery or procedure. [2021]

9. Japan pubmed.ncbi.nlm.nih.gov

Perioperative management of patients with atrial fibrillation receiving anticoagulant therapy. [2020]