Perioperative Anticoagulant Use for Surgery Evaluation -Virtual Visit (PAUSE-Virtual)

Recruiting

• Conditions: Atrial Fibrillation (AF)

• Registration Number: NCT06844227
• Lead Sponsor: McMaster University

Brief Summary

The purpose of the PAUSE-Virtual Study is to show that by changing pre-surgery visits with patients taking a blood thinner (direct oral anticoagulant (apixaban, dabigatran, edoxaban, rivaroxaban or warfarin) when the participant requires elective surgery, using a standard, in-person proven approach, to a virtual visit, either telephone or video conference, is as safe. Patients who are receiving a blood thinner for the medical condition known as atrial fibrillation (AF) and require an elective surgery/procedure, is common. These patients have to stop taking their blood thinner for a certain time before the procedure to reduce serious complications of stroke or bleeding. For doctors who help manage these patients before a procedure, appointments have been traditionally done in-person. Patients receive instructions about when to stop and restart their blood thinners and taught how to self-administrator a short acting blood thinner (heparin) if needed. The COVID pandemic changed the way these appointments were done, making it important to contact these patients without them having to come to the hospital for an in person visit. Virtual patient care, by telephone or video conference, to communicate to patients about when to start and restart their blood thinner was necessary. This study wants to show that this virtual method of instruction, using a standardized plan of managing patient care, is easy, acceptable to patients and as safe when compared to an in-person meeting. Such instruction would also be cost-efficient standard post-pandemic. Prior work has shown that both a standard care of patients who are receiving blood thinners and a point-of-care decision "app", available through Thrombosis Canada (www.thrombosiscanada.ca) website, have been trusted during this virtual visit successfully. The investigator will show, by following up at 30 days, that this standardized management plan is safe and can be done virtually, with a low risk of stroke and major bleeding.

Detailed Description

The Clinical Problem: The management of patients who are taking warfarin or a direct oral anticoagulant (DOAC) and need an elective surgery/procedure is a common and important clinical problem: (i) \~200,000 patients/yr are assessed in Canada for such management and this will increase due to an ageing population and an increase in anticoagulant use; and (ii) if anticoagulants are not managed carefully, with evidence-based protocols, patients can be exposed to an increased risk for disabling stroke if anticoagulant interruption is too long or life-threatening bleeding if interruption is too short.

The Healthcare Delivery Problem: Perioperative management of anticoagulant therapy has been traditionally done in an in-person setting where patients receive instructions about when to stop and restart anticoagulants and, if needed, to receive teaching to self-administer heparin bridging. The COVID pandemic has upended this healthcare delivery model, necessitating virtual management by phone/video. Virtual patient care to manage perioperative anticoagulation has the potential to be an efficient and patient-friendly standard post-pandemic. However, to attain this objective, it must be reliably shown that virtually-administered, standardized, perioperative anticoagulation management is: (i) safe, with acceptably low rates of stroke and bleeding; (ii) easy to apply in practice; and (iii) acceptable to patients.

The foundation for this study is based on prior work by the investigator: (i) The investigator has led multicenter clinical trials (BRIDGE, PAUSE) that provide benchmarks for safe perioperative management of patients who are receiving warfarin or a DOAC; (ii) the management protocols from these trials were incorporated into a clinical decision tool that is available (cost-free) by Thrombosis Canada (www.thrombosiscanada.ca). This point-of-care app allows input of patient-specific information to manage individual patients with atrial fibrillation/flutter (AF) who are receiving warfarin or a DOAC and require an elective surgery/procedure. At the end of the assessment, a care-path summary is available as a PDF for clinicians and patients for downloading and printing.

The Opportunity: The pandemic has necessitated the adoption of virtual perioperative anticoagulant management but also has provided the opportunity to re-evaluate how such care can be safely delivered. Given that (i) perioperative anticoagulant interruption/resumption and heparin bridging protocols are standardized, and (ii) there is an easy-to-use, point-of-care, management app available, the investigator has a unique opportunity to apply evidence-informed protocols with user-friendly knowledge translation tools to assess the safety and acceptability to patients of virtual perioperative anticoagulant management.

The Solution: A prospective cohort study (non-RCT) assessing standardized virtual perioperative management in 2 cohorts of patients on warfarin or a DOAC who require an elective surgery/procedure.

Hypothesis \& Postulates: (i) the investigator hypothesizes that virtual perioperative management will be safe for patient care, with 30-day postoperative rates of stroke/systemic embolism (SSE) ≤0.5% and major bleeding (MB) ≤1.5%. With a sample size of 847 patients in Cohort 1 and in Cohort 2, the investigator will have 90% power at the 95% level of significance to reject the null hypothesis that the observed rates are ≥1.5% for SSE and ≥3% for MB in each cohort. (ii) The investigator postulates (a) that virtual management will be as safe as in matched historical control groups who received benchmark in-person management, (b) that virtual management will reduce healthcare costs and costs to patients, and (c) that patients will be satisfied with virtual management and will be willing to receive this methods of healthcare delivery post-pandemic.

Significance: PAUSE-Virtual will shift perioperative anticoagulant management from a resource-intensive in-person model to a patient-friendly virtual model, establishing a standard-of-care option for 200,000 patients/yr in Canada. The investigator is a leading group in perioperative anticoagulant management worldwide, having done the landmark BRIDGE1 and PAUSE2 trials. There is no other research group (that the investigator knows of) that will do this trial, and it will not be funded by industry (no commercial interest).

Study Timeline

• Study Start: 2021-12-01
• Status Verified: 2024-11
• Study First Submitted: 2024-11-25
• Study First Submitted QC: 2025-02-19
• Study First Posted: 2025-02-25
• Last Update Submitted: 2025-03-05
• Last Update Posted: 2025-03-10
• Primary Completion: 2025-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1780

Inclusion Criteria

• Age 18 years of age or older with AF/flutter (chronic, persistent, paroxysmal) that requires anticoagulation
• Receiving warfarin, with a target international normalized ratio (INR) range of 2.0-3.0, or a DOAC, comprising one of the following regimens: apixaban, 2.5 mg or 5 mg bid; edoxaban, 30 mg or 60 mg daily; dabigatran, 110 mg or 150 mg bid; or rivaroxaban, 15 mg or 20 mg daily
• Require an elective (planned, non-urgent) surgery or invasive medical or surgical procedure

Exclusion Criteria

• Indication for anticoagulation is not AF/flutter (e.g., mechanical heart valve, VTE, other)
• Non-standard anticoagulant regimen used (e.g., warfarin INR 3-4, rivaroxaban 2.5 mg bid)
• In DOAC users only: creatinine clearance <25 mL/min (that preclude DOAC use)
• Cognitive impairment or psychiatric illness (that precludes reliable contact during follow-up)
• Unable or unwilling to provide consent for virtual care (in-person care will be provided)
• Previous participation in this study for an elective surgery/procedure

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary Outcome	From enrollment to end of 30 day follow up	The investigator will determine 30-day post-procedure event rates with 95% confidence interval (CIs) for stroke/systemic embolism (SSE), major bleeding (MB) and, with a one-sided binomial test, will determine in Cohort 1 and Cohort 2 if the SSE rate is lower than 1.5%, and the MB rate is lower than 3%. The investigator will compare patient demographic (e.g., age, gender) and clinical characteristics (e.g., surgery type, SSE/MB risk) in Cohort 1 vs. Control 1 and Cohort 2 vs. Control 2 using Fisher's exact test, respectively, so as to compare SSE and MB in Cohorts and Controls, adjusting for key covariates (e.g., surgery type, anticoagulant type, gender) using multivariate logistic regression. The investigator will determine the proportions (and 95% CIs) for patient satisfaction categories in virtual care and willingness to receive future virtual care.

Secondary Outcome Measures

Name	Time	Method
Secondary Outcome 1	From enrollment to end of 30 day follow up	To demonstrate that virtual management is safe, as defined by 30-day postoperative rates of stroke/systemic embolism (SSE) of ≤0.5% and major bleeding (MB) of ≤1.5% with ability to exclude rates of SSE and MB of 1.5% and 3.0%, with a sample of 847 patients in Cohorts 1 and 2, the investigator will have 90% power at the 95% level of significance to reject the null hypothesis that the observed rate of SSE is ≥1.5% and MB is ≥3.0%. This sample size of 847 is increased by 5% to 890 patients per Cohort (1,780 total) to account for cancelled surgeries/procedures and patients lost to follow-up.
Secondary Outcome 2	From enrollment to end of 30 day follow up	The investigator will determine the cost effectiveness of the virtual management compared with in-person care from both public payer and societal perspectives. Health resource use will be collected alongside the clinical data collection that includes physician, nursing and pharmacist consultation time, medication, diagnostics and procedures, and hospitalization. Patient's time and travel costs will also be included in the analysis from the societal perspective. Incremental cost effectiveness ratio between each of the cohort and corresponding control group will be calculated. 95% confidence interval of the ratio will be estimated using non-parametric bootstrapping approach. Cost effectiveness acceptability curves will be used to show the probability of virtual care being cost effective compared with in person care over a wide range of willingness-to-pay values.

Trial Locations

Locations (10)

Endeavor Health - Northshore; 🇺🇸 Evanston, Illinois, United States

Henry Ford; 🇺🇸 Detroit, Michigan, United States

Northwell Health; 🇺🇸 Great Neck, New York, United States

Thomas Jefferson University Hospital; 🇺🇸 Philadelphia, Pennsylvania, United States

QEII Health Sciences Centre; 🇨🇦 Halifax, Nova Scotia, Canada

Hamilton General Hospital; 🇨🇦 Hamilton, Ontario, Canada

St. Joesph's Healthcare; 🇨🇦 Hamilton, Ontario, Canada

Juravinski; 🇨🇦 Hamilton, Ontario, Canada

The Ottawa Hospital; 🇨🇦 Ottawa, Ontario, Canada

Larissa University Hospital; 🇬🇷 Larisa, Greece