Early Identification of SEPsis SIGNs in Emergency Department (SepSIGN)

Objective of SepSIGN project is to validate biomarkers able to predict the clinical worsening of patients freshly admitted at Emergency Department. Targeted population is adult patients, freshly admitted at ED, with a suspected or confirmed infection.

Study Overview

• Status: Completed
• Conditions: Sepsis; Infection

Detailed Description

Sepsis is an important health issue with considerable socio-economic consequences. In 2017, the World Health Association made sepsis a global health priority, and has adopted a resolution to improve the prevention, diagnosis, and management of sepsis.

Over the last decade, a decrease in the mortality rate has been observed; in particular thanks to improved management, more appropriate intervention approaches in the Emergency Department (ED) and better recognition of organ failure. This statement is based on qSOFA and SOFA scores from the international Sepsis-3 definition. Sepsis-3 can help front-line clinicians detect severe patients with a higher risk of mortality but does not predict the clinical deterioration especially in patients without initial organ dysfunction. Furthermore, studies still demonstrate that 20% of patients with infection or uncomplicated sepsis experience disease worsening within 72 hours after ED admission.

Symptoms and signs of sepsis are variable and this makes clinical recognition and assessment very difficult in particular on Emergency Department (ED) patients due to their infectious illness background and the frequent comorbidities.

Unfortunately, as of today, no biological marker has yet been validated to appropriately predict early deterioration in unselected patients admitted to the ED with acute infection, irrespective of their clinical presentation. Physiology of sepsis is complex and some underlying dysfunction could already exist in the early phase of sepsis before patients meet diagnostic criteria. Thus, patients may be clinically asymptomatic at the origin of organ failure. As a result, doubtful patients are often over-hospitalized while they could be treated at home, leading to overcrowding and extra costs for hospitals In these conditions, the main challenge of ED clinicians is differentiating mild infections from life-threatening ones in the heavy workload of ED environment. Objective of SepSIGN project is to validate biomarkers able to predict the clinical worsening of patients freshly admitted at Emergency Department. Targeted population is adult patients freshly admitted at ED, whom blood samples will serve to validate candidate markers.

• Study Type: Observational
• Enrollment (Actual): 815

Contacts and Locations

Study Locations

• France
  • Aurillac, France, 15000
    • CH Henri Mondor Aurillac
  • La Tronche, France, 38700
    • Chu Grenoble Alpes
  • Limoges, France, 87000
    • CHU Dupuytren
  • Lyon, France, 69003
    • Hôpital Edouard Herriot, HCL
  • Montauban, France, 82000
    • CH de Montauban
  • Paris, France, 75012
    • Hôpital Saint-Antoine AP-HP
  • Tours, France, 37044
    • Hôpital Trousseau CHRU
• Monaco
  • Monaco, Monaco, 98000
    • Centre Hospitalier Princesse Grace
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Vanderbilt University Medical Center
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patient freshly admitted to Emergency department

Description

Inclusion Criteria:

All of the following criteria:

• Delay between ED presentation and inclusion must not exceed 12h
• Age 18 years or greater
• Acute infection suspected or confirmed

• That fulfills at least two of the following systemic inflammatory response syndrome (SIRS) criteria:

  • Temperature > 38°C (100.4°F) or < 36°C (96.8°F)
  • Heart rate > 90 bpm
  • Respiratory rate > 20 cycles/min or PaCO2 < 32 mmHg
  • Leukocyte > 12000/mm3 or < 4000/mm3 or 10% bands
• With a delta SOFA < 2 from baseline

• At Risk for deterioration defined as:

  1. any patient that the emergency department physician has admitted or intends to admit as an inpatient* to the hospital.
  2. patients discharged home (outpatient**) who are either i) >65 years old or ii) diagnosed with pneumonia

Exclusion Criteria:

• Unable to obtain a valid and written consent from a patient or their legally authorized representative in accordance with the local regulatory instances (this include in FR: Person not affiliated to a health insurance scheme, or not a beneficiary of such a scheme. Persons who are the subject of a legal protection order. Person with restricted freedom following a legal or administrative decision and a person admitted without their consent pursuant to Articles L.3212-1 and 3213-1, which are not included in Article L.1122-8 of the French Public Health Code.)
• Known pregnancy, in labor or breastfeeding
• Patients with isolated uncomplicated pharyngitis, sinusitis, or otitis media
• Infectious symptoms present for > 5 days prior to presentation

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of patients with deterioration within 72-hour period following T0 (enrollment)	clinical deterioration of a patient at any time during the 72-hour period following T0 (enrollment), which is defined as any of the following: increase of SOFA score ≥ 2 points; need of new organ support (respiratory, circulatory, renal); death An Endpoint Adjudication Committee (EAC) composed of acute care specialists will apply these criteria. This EAC will also confirm /exclude the presence of infection at T0 (enrollment) based on all information available in eCRF.	Up to 72 hours after admission

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants that have been re-admission	Re-admission in hospital any time from T0 to T72h (for patients who have been admitted) OR Admission any time from T0 to T72h (for patients who were discharged from the emergency department)	Up to 28 days after admission
Number of patients with Early and late mortality	Early and late mortality defined by vital status of patients (alive or dead) at Day 28. This information will be collected on the associated eCRF or obtained using follow up procedures (including telephone call) for the patients discharged.	Up to 28 days after admission
number of patients with confirmed bacterial and viral infection	the adjudication committee will also confirm site of infection and diagnosis of infection A. Confirmed sites of infections B. Infection status (Infection DEFINITELY present / Infection LIKELY present / Infection LIKELY NOT present / NON INFECTIOUS diagnosis identified) C. Viral versus bacterial infections	Up to 28 days after admission

Collaborators and Investigators

• Sponsor: BioMérieux
• Collaborators: Vanderbilt University Medical Center; Centre d'Investigation Clinique - Limoges

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2020
• Primary Completion (Actual): May 2, 2022
• Study Completion (Actual): May 2, 2022

Study Registration Dates

• First Submitted: February 6, 2020
• First Submitted That Met QC Criteria: February 6, 2020
• First Posted (Actual): February 10, 2020

Study Record Updates

• Last Update Posted (Actual): June 1, 2023
• Last Update Submitted That Met QC Criteria: May 31, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Infection; Emergency Department; Sepsis; Worsening
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Disease Attributes; Sepsis; Toxemia; Emergencies
• Other Study ID Numbers: SepSIGN

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No