Adverse Drug Events in Patients on Oral Anticoagulation in the Emergency Department (ADEOA)

Real-life Epidemiology of Adverse Drug Events in Patients on Oral Anticoagulation in the Emergency Department Setting

Rationale:

According to the latest National Survey on Care-Related Adverse Events, anticoagulants, including vitamin K antagonists (VKAs), rank first among medications responsible for serious iatrogenic accidents (37% in 2004, 31% in 2009). The EMIR study (2007) showed that VKAs were the leading cause of hospitalization for adverse effects (12.3%), with approximately 5,000 fatal hemorrhage-related accidents annually. Treatment and prevention of thromboembolic events represent a major public health challenge due to increased mortality, severity of functional sequelae, growing number of patients requiring treatment, and medical, social, and economic consequences. In 2013, an estimated 3.12 million patients received anticoagulation (4-5% of the French population). Several types of adverse events under oral anticoagulation appear to have high incidence in emergency settings: traumatic hemorrhage, spontaneous hemorrhage, asymptomatic overdose, and thrombosis. Different variables are associated with these events in patients admitted to emergency departments under oral anticoagulant treatment, but few studies have been conducted in real-world settings with large patient samples.

Hypothesis:

Iatrogenic events have a high incidence in patients admitted to emergency departments under oral anticoagulants and are a factor in early and late morbidity and mortality.

Primary Objective:

To describe the characteristics of patients admitted to the emergency department on oral anticoagulant therapy, with a particular focus on characterizing those presenting with Adverse Drug Events (ADEOA).

Study Design:

• Type: Observational, descriptive study
• Duration: 36 months total (24 months for data collection, 12 months for analysis)
• Sample Size: Estimated 2,080 patients (approximately 20 patients/week over 2 years)

Inclusion Criteria:

• Age ≥18 years
• Admission to adult emergency department
• Study period: January 1, 2018 to December 31, 2019

• Current oral anticoagulation therapy with:

  • Acenocoumarol (Sintrom®/Minisintrom®)
  • Apixaban (Eliquis®)
  • Dabigatran (Pradaxa®)
  • Fluindione (Previscan®)
  • Rivaroxaban (Xarelto®)
  • Warfarin (Coumadine®)

Exclusion Criterion:

- Discontinuation of anticoagulant therapy for more than 24 hours

Primary Outcome Measures:

1. Description of oral anticoagulant groups based on medication type

2. Characterization of Adverse Drug Events in Patients on Oral Anticoagulation in the Emergency Department (ADEOA):

   1. Presence of ADEOA:

      • Traumatic hemorrhage: acute bleeding following recent trauma
      • Spontaneous hemorrhage: acute bleeding unrelated to recent trauma
      • Asymptomatic overdose: INR >3 for vitamin K antagonist patients
      • Thrombosis: new arterial or venous thrombosis despite ongoing anticoagulation
   2. Absence of ADEOA

Secondary Outcome Measures:

1. Assessment of adherence to oral anticoagulant prescribing guidelines
2. Identification of etiological factors for anticoagulation-related adverse events
3. Identification of early morbidity and mortality risk factors
4. Evaluation of medical-economic impact of adverse events and cost-effectiveness analysis of adverse events
5. Quality of life assessment

Study Overview

• Status: Recruiting
• Conditions: Hemorrhage; Thrombosis; Anticoagulant Therapy; Traumatic Hemorrhage

• Study Type: Observational
• Enrollment (Estimated): 2080

Contacts and Locations

• Study Contact: Name: Omide TAHERI, MD, PhD; Phone Number: 03 81 66 70 28; Email: omide.taheri@gmail.com
• Study Contact Backup: Name: Thibaut DESMETTRE, MD, PhD; Email: thibaut.desmettre@hug.ch

Study Locations

• France
  • Besançon, France
    • Recruiting
    • CHU Besançon
    • Contact: Omide TAHERI, MD, PhD; Phone Number: 03 81 66 70 28; Email: omide.taheri@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Adult patients on oral anticoagulation therapy admitted to the emergency department

Description

Inclusion Criteria:

• Age ≥18 years
• Admission to adult emergency department of Besançon University Hospital
• Study period: January 1, 2018 to December 31, 2019

• Current oral anticoagulation therapy with:

  • Acenocoumarol
  • Apixaban
  • Dabigatran
  • Fluindione
  • Rivaroxaban
  • Warfarin

Exclusion Criterion:

- Discontinuation of anticoagulant therapy for more than 24 hours

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Oral anticoagulant therapy; anti-vitamin K or direct oral anticoagulants therapy
No oral anticoagulant therapy; no anti-vitamin K or direct oral anticoagulants therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Description of oral anticoagulant groups based on medication type	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterization of Iatrogenic Events Related to Oral Anticoagulants (ADEOA)	Traumatic hemorrhage: acute bleeding following recent trauma; Spontaneous hemorrhage: acute bleeding unrelated to recent trauma; Asymptomatic overdose: INR >3 for vitamin K antagonist patients; Thrombosis: new arterial or venous thrombosis despite ongoing anticoagulation	1 day
Assessment of adherence to oral anticoagulant prescribing guidelines		1 day
Identification of etiological factors for anticoagulation-related adverse events		1 day
Identification of early morbidity and mortality risk factors		1 year
Evaluation of medical-economic impact of adverse events		1 year

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Besancon
• Investigators: Study Chair: Frédéric MAUNY, MD, PhD, CHU Besançon; Study Chair: Marc PUYRAVEAU, MSc, CHU Besançon

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: November 14, 2024
• First Submitted That Met QC Criteria: November 14, 2024
• First Posted (Estimated): November 18, 2024

Study Record Updates

• Last Update Posted (Estimated): November 18, 2024
• Last Update Submitted That Met QC Criteria: November 14, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: epidemiology; hemorrhage; Thrombosis; emergency department; mortality; anticoagulant therapy; emergency medicine; oral anticoagulant; Traumatic hemorrhage; Spontaneous hemorrhage; Asymptomatic overdose
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Disease Attributes; Chemically-Induced Disorders; Embolism and Thrombosis; Emergencies; Thrombosis; Drug-Related Side Effects and Adverse Reactions; Hemorrhage
• Other Study ID Numbers: 2024/920

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No