PAUSE-ER: Perioperative Anticoagulant Use for Surgery Evaluation Emergency Registry

Sponsor

McMaster University (Other)

Overall Status

Unknown status

CT.gov ID

NCT04195113

Collaborator

Hamilton Health Sciences Corporation (Other), St. Joseph's Healthcare Hamilton (Other)

400

Enrollment

Locations

35.8

Anticipated Duration (Months)

133.3

Patients Per Site

3.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation Venous Thromboembolism Arterial Vascular Disease

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 Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

400 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Aug 7, 2019

Anticipated Primary Completion Date :

Aug 1, 2022

Anticipated Study Completion Date :

Aug 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
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.

Outcome Measures

Primary Outcome Measures

Number of patients who had arterial thromboembolism (ATE) [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.
Number of patients who had venous thromboembolism (VTE) [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).
Number of patients who had major bleeding [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
Number of patients who died [Each patient will be followed-up once 30±7-days post-operative]
Death due to any cause

Secondary Outcome Measures

Number of patients who received adjunctive hemostatic therapies [Each patient will be followed-up once 30±7-days post-operative]
For example, prothrombin complex concentrates, FEIBA, tranexamic acid, etc.
Number of patients who received specific anticoagulant reversal agents [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.
Number of patients who received blood products [Each patient will be followed-up once 30±7-days post-operative]
For example, packed red blood cells, platelets, plasma, cryoprecipitate, fibrinogen, etc.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)