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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines two methods of managing blood thinners for individuals with atrial fibrillation (irregular heartbeats) or venous thromboembolism (blood clots) who require high-risk surgery. The goal is to determine if the new method is as safe as the usual one in maintaining low blood thinner levels before surgery. The trial focuses on patients taking medications such as Apixaban, Dabigatran, Rivaroxaban, or Edoxaban. Individuals with atrial fibrillation or blood clots planning high-risk surgery might be suitable candidates for this trial. As an unphased trial, it offers participants the chance to contribute to research that could enhance surgical outcomes for similar patients.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the treatments studied in this trial—Apixaban, Dabigatran, Rivaroxaban, and Edoxaban—are generally safe when used carefully. Studies indicate that Apixaban may cause significant bleeding in about 3 out of 100 patients undergoing high-risk procedures. Dabigatran presents a slightly lower risk, with major bleeding occurring in fewer than 1 out of 100 patients in similar situations. Rivaroxaban affects about 1 to 2 out of 100 patients with major bleeding, demonstrating good tolerance with proper use. Edoxaban also shows low rates of major bleeding and other serious issues, making it a safe choice for many. These medications have been extensively studied and are approved for other uses, supporting their safety. Always consult a doctor to understand the specific risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it's exploring new ways to manage anticoagulants for patients with atrial fibrillation or venous thromboembolism who need high-risk surgeries or procedures. Usually, managing these blood thinners around surgery is tricky, due to bleeding risks and the need to prevent clots. The trial is comparing two protocols, ASRA and PAUSE, which aim to balance these risks more effectively. By refining these management strategies, the trial could lead to safer surgical outcomes and improve the overall care for patients needing these critical medications.

What evidence suggests that this trial's treatments could be effective for atrial fibrillation?

This trial will compare different perioperative anticoagulant management strategies for patients with atrial fibrillation undergoing high bleed risk surgery. Research has shown that apixaban, one of the treatments in this trial, effectively lowers the risk of stroke and blood clots in patients with atrial fibrillation (AF), with major bleeding after surgery reported to be low, around 1.35%. Dabigatran, another treatment option in this trial, also shows promise, with even lower major bleeding rates of about 0.90% in some cases. Rivaroxaban, also under study in this trial, matches warfarin in effectiveness, with low rates of stroke and major bleeding, usually between 0.2% and 1.9%. Edoxaban, the fourth treatment being tested, performs well too, with major heart-related issues occurring in only about 2.4% of cases after surgery. Overall, these treatments aim to manage blood clot risks effectively while ensuring safety during surgery. ^{3 6 7 8 9}

Who Is on the Research Team?

James Douketis, MD

Principal Investigator

McMaster University/St. Joseph's Healthcare

Joseph Shaw, MD

Principal Investigator

The Ottawa Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6686768/

Perioperative Management of Patients With Atrial Fibrillation ... The 30-day postoperative rate of major bleeding was 1.35% (95% CI, 0%-2.00%) in the apixaban cohort, 0.90% (95% CI, 0%-1.73%) in the dabigatran cohort

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1302507

Oral Apixaban for the Treatment of Acute Venous ... The primary efficacy outcome of recurrent venous thromboembolism occurred in 59 of 2609 patients (2.3%) in the apixaban group and in 71 of 2635 (2.7%) in the ...

3. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.118.035418

Outcomes Associated With Apixaban Use in Patients ... Among patients with ESKD and AF on dialysis, apixaban use may be associated with a lower risk of major bleeding compared with warfarin.

4. ashpublications.org ashpublications.org/blood/article/124/25/3692/33595/Management-and-clinical-outcomes-in-patients

Management and clinical outcomes in patients treated with ... During the 30 days postprocedure, stroke or systemic embolism occurred after 16/4624 (0.35%) procedures among apixaban-treated patients and 26/ ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0090825824000659

Efficacy, safety, and feasibility of Apixaban for ... 30-day venous thromboembolism (VTE) rate was lower in the apixaban (0.6%) compared to enoxaparin group (6.2%) (aOR 0.13). · 90-day VTE rate was 2.7% and 6.2% in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10847030/

Perioperative management of apixaban in patients with ... The indication for anticoagulation was AF for most patients (41/49; 83.7%) and VTE for the remainder; median CHA2DS2-VASc score for AF patients ...

7. jamanetwork.com jamanetwork.com/journals/jamainternalmedicine/fullarticle/2740207

Perioperative Management of Patients With Atrial ... In patients with a high–bleeding-risk procedure, the rates of major bleeding were 2.96% (95% CI, 0%-4.68%) in the apixaban cohort and 2.95% (95% ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S1538783622182553

Thrombotic and bleeding outcomes following the ... We found a low 30-day risk of postoperative arterial thromboembolic events and major bleeding. •. Contemporary perioperative anticoagulation practices appear ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT06957366

Perioperative Anticoagulant Use for Surgery Evaluation -2 ... Patients currently taking Apixaban that have atrial fibrillation or Venous Thromboembolism and require an elective high bleed risk surgery or neuraxial ...