Clinical trial NCT04195113: Perioperative Anticoagulant Use for Surgery Evaluation Emergency Registry
Official title: Management and Outcomes of Patients Receiving Oral Anticoagulants Who Require an Urgent/Emergency Surgery or Procedure: A Prospective Registry Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Atrial Fibrillation
Venous Thromboembolism
Arterial Vascular Disease
Keywords: anticoagulant
atrial fibrillation
venous thromboembolism
arterial vascular disease
surgery
oral anticoagulant
blood thinner
warfarin
DOAC
interruption
discontinue
emergency
perioperative
vitamin k antagonist
Lead sponsor: McMaster University
Sponsor class: OTHER
Collaborators: name: Hamilton Health Sciences Corporation
name: St. Joseph's Healthcare Hamilton
First posted: 2019-12-11
Enrollment: 242
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Study cohort will be recruited from urgent care and/or emergency department populations.

Brief summary: 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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Number of patients who had arterial thromboembolism (ATE)
timeFrame: Each patient will be followed-up once 30±7-days post-operative
measure: Number of patients who had venous thromboembolism (VTE)
timeFrame: Each patient will be followed-up once 30±7-days post-operative
measure: Number of patients who had major bleeding
timeFrame: Each patient will be followed-up once 30±7-days post-operative
measure: Number of patients who died
timeFrame: Each patient will be followed-up once 30±7-days post-operative
Secondary outcomes:
measure: Number of patients who received adjunctive hemostatic therapies
timeFrame: Each patient will be followed-up once 30±7-days post-operative
measure: Number of patients who received specific anticoagulant reversal agents
timeFrame: Each patient will be followed-up once 30±7-days post-operative
measure: Number of patients who received blood products
timeFrame: Each patient will be followed-up once 30±7-days post-operative
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
city: Hamilton
country: Canada
facility: Juravinski Hospital
state: Ontario
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare Hamilton
state: Ontario
Study officials:
affiliation: McMaster University
name: Deborah Siegal, MD MSc FRCPC
role: PRINCIPAL_INVESTIGATOR
affiliation: McMaster University
name: James Douketis, MD MSc FRCPC
role: PRINCIPAL_INVESTIGATOR
References: