Perioperative Anticoagulant Use for Surgery Evaluation Emergency Registry (PAUSE-ER)

April 28, 2023 updated by: Deborah Siegal, McMaster University

Management and Outcomes of Patients Receiving Oral Anticoagulants Who Require an Urgent/Emergency Surgery or Procedure: A Prospective Registry Study

Among patients who are receiving long-term anticoagulant therapy, whether with a direct oral anticoagulant (DOAC) or vitamin K antagonist (VKA), approximately 3-5% who require treatment interruption for a surgery will do so in an urgent/emergency surgery setting. Additionally, there is considerable morbidity and mortality associated with DOAC/VKA management in an urgent/emergency surgery setting. Thus, this prospective registry study aims to identify and compare determinants for perioperative adverse events in DOAC-treated and VKA-treated patients who require an urgent/emergency surgery, and to identify which of these are modifiable. It also aims to describe and compare management of anticoagulant reversal (i.e., non-specific and specific reversal agents) and resource utilization (i.e., blood transfusion) in DOAC- and VKA-treated patients who need an urgent/emergency surgery.

Study Overview

Status

Completed

Conditions

Detailed Description

Among patients who are receiving long-term anticoagulant therapy, whether with a direct oral anticoagulant (DOAC) or vitamin K antagonist (VKA), approximately 3-5% who require treatment interruption for a surgery will do so in an urgent/emergency surgery setting. Assuming that approximately 500,000 to 800,000 patients per year in the U.S. and E.U. will require perioperative management for a surgery/procedure, the investigators estimate that approximately 20,000 to 25,000 patients will require an urgent/emergency surgery. Although this represents a small proportion of patients who require anticoagulant interruption, there is considerable morbidity and mortality associated with DOAC/VKA management in an urgent/emergency surgery setting. Thus, for VKA-treated patients, rates of thromboembolism, major bleeding and mortality are 10.5%, 22.9%, and 2.9%, respectively. Similarly, for DOAC-treated patients who require an urgent/emergency surgery, rates of thromboembolism, major bleeding and mortality are 7.4%, 17.6%, and 1.5%, respectively. By comparison, rates of these outcomes for DOAC/VKA-treated patients who need elective surgery are ~0.5-1.0%, ~1-3%, and <0.5%, respectively. Most studies have focused on the perioperative anticoagulant management of patients who require an elective surgery/procedure. To the investigators' knowledge, few studies have focused on the assessment of adverse outcomes in an urgent/emergency perioperative setting among anticoagulated patients. Thus, this prospective registry study aims to 1) identify and compare determinants for perioperative adverse events in DOAC-treated and VKA-treated patients who require an urgent/emergency surgery, and to identify which of these are modifiable, and 2) describe and compare management of anticoagulant reversal (i.e., non-specific and specific reversal agents) and resource utilization (i.e., blood transfusion) in DOAC- and VKA-treated patients who need an urgent/emergency surgery. The data gained from this study will generate hypotheses for subsequent prospective studies that would potentially assess different management strategies in this clinical setting (e.g., use of DOAC antidote- vs. prothrombin complex concentrate-based management).

Given the exploratory, hypothesis-generating nature of the proposed study, the sample size is one of convenience, comprising 200 DOAC- and 200 warfarin-treated patients. Patients will be recruited from 30 clinical sites in Canada, the US, and Europe. With 30 clinical sites, the investigators estimate that 3-5 patients/month (60-72/yr) per arm can be recruited, corresponding to an overall rate of 180-216 over 3 years. Each study patient will participate for approximately 4 weeks, with one follow-up phone call at 4 weeks post-procedure.

Study Type

Observational

Enrollment (Actual)

242

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Hamilton, Ontario, Canada
        • Hamilton General Hospital
      • Hamilton, Ontario, Canada
        • Juravinski Hospital
      • Hamilton, Ontario, Canada
        • St. Joseph's Healthcare Hamilton

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Study cohort will be recruited from urgent care and/or emergency department populations.

Description

Inclusion Criteria:

  • Adult (age ≥18 years) receiving a DOAC (dabigatran, rivaroxaban, apixaban or edoxaban) or a VKA (warfarin) for stroke prevention atrial fibrillation/flutter, treatment or secondary prevention of venous thromboembolism or treatment of arterial vascular disease.
  • Requires an urgent or emergency surgery and planned surgery is scheduled within 72 hours from the time the decision was made to proceed to surgery (e.g. time of assessment in emergency department, or time of consultation note etc.) or if the time of the decision to proceed to surgery is unavailable, from the time from admission to surgery; or urgent surgery as deemed by Investigator.
  • Patient or delegate is willing and able to provide written informed consent while patient is hospitalized and agree to telephone follow-up 30 days (±7 days) after surgery.

Exclusion Criteria:

  • Patient receiving a non-warfarin VKA.
  • Patient enrolled in the study previously and had the urgent procedure/surgery (if procedure/surgery cancelled, patient can re-enroll)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Direct Oral Anticoagulants (DOACs)
In this study, DOACs include apixaban, dabigatran, edoxaban and/or rivaroxaban.
Vitamin K Antagonist (VKA)
In this study, the VKA is warfarin.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients who had arterial thromboembolism (ATE)
Time Frame: Each patient will be followed-up once 30±7-days post-operative

Any of the following: stroke, systemic arterial embolism, and/or myocardial infarction.

  • 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 intraoperatively or by objective imaging (e.g., CT angiography).
  • Myocardial Infarction: Symptomatic myocardial ischemia, defined by pre-specified clinical and objective EKG- and/or troponin-related criteria.
Each patient will be followed-up once 30±7-days post-operative
Number of patients who had venous thromboembolism (VTE)
Time Frame: Each patient will be followed-up once 30±7-days post-operative
Any of the following: symptomatic deep vein thrombosis and/or pulmonary embolism, confirmed by objective imaging studies (e.g., ultrasound, CT pulmonary angiogram, VQ scan).
Each patient will be followed-up once 30±7-days post-operative
Number of patients who had major bleeding
Time Frame: Each patient will be followed-up once 30±7-days post-operative

As defined by the International Society on Thrombosis and Haemostasis (ISTH), ≥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 once 30±7-days post-operative
Number of patients who died
Time Frame: Each patient will be followed-up once 30±7-days post-operative
Death due to any cause
Each patient will be followed-up once 30±7-days post-operative

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients who received adjunctive hemostatic therapies
Time Frame: Each patient will be followed-up once 30±7-days post-operative
For example, prothrombin complex concentrates, FEIBA, tranexamic acid, etc.
Each patient will be followed-up once 30±7-days post-operative
Number of patients who received specific anticoagulant reversal agents
Time Frame: Each patient will be followed-up once 30±7-days post-operative
For example, idarucizumab (for dabigatran), andexanet alfa (for factor Xa inhibitors), vitamin K (for VKA), prothrombin complex concentrates (for VKA) etc.
Each patient will be followed-up once 30±7-days post-operative
Number of patients who received blood products
Time Frame: Each patient will be followed-up once 30±7-days post-operative
For example, packed red blood cells, platelets, plasma, cryoprecipitate, fibrinogen, etc.
Each patient will be followed-up once 30±7-days post-operative

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

McMaster University

Collaborators

St. Joseph's Healthcare Hamilton
Hamilton Health Sciences Corporation

Investigators

  • Principal Investigator: Deborah Siegal, MD MSc FRCPC, McMaster University
  • Principal Investigator: James Douketis, MD MSc FRCPC, McMaster University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 7, 2019

Primary Completion (Actual)

December 31, 2022

Study Completion (Actual)

December 31, 2022

Study Registration Dates

First Submitted

December 9, 2019

First Submitted That Met QC Criteria

December 9, 2019

First Posted (Actual)

December 11, 2019

Study Record Updates

Last Update Posted (Actual)

May 1, 2023

Last Update Submitted That Met QC Criteria

April 28, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PAUSE-ER-2019

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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