Towards Novel BIOmarkers to Diagnose SEPsis on the Emergency Room (BIOSEP)

Objectives:

1. To compare the immune response of patients with or without sepsis presenting to the ED with a(n) (suspected) infection.
2. To determine immune response aberrations that are associated with an increased risk of developing sepsis in patients presenting to the ED with a(n) (suspected) infection without sepsis.
3. To determine the long term cognitive and physical sequelae of sepsis after admission.

Study Overview

• Status: Recruiting
• Conditions: Infections; Sepsis; Septic Shock; Infection, Bacterial; Sepsis, Severe; Infection Viral; Infections, Respiratory
• Intervention / Treatment: Other: No intervention

Detailed Description

Sepsis will be defined in accordance with the current Sepsis 3.0 criteria as a(n) (suspected) infection with evidence of organ failure, as reflected by a SOFA (Sequential Organ Failure Assessment) score of ≥2. Notably, a molecular definition of sepsis does not exist and there is no pathological gold standard; therefore, in accordance with the current international consensus, the investigators consider the commonly used clinical organ failure (SOFA) criteria as the best option. The SOFA score is composed of six organ dysfunctions (cardiovascular, pulmonary, renal, hepatic, coagulation and neurological). The SOFA score was developed for ICU patients, but its components can be easily scored in an ED (and hospital ward) setting with the exception of the pulmonary component; this pulmonary dysfunction score is based on the PaO2/FiO2 (PF) ratio, wherein PaO2 is the partial pressure of oxygen in arterial blood and FiO2 the fraction of inspired oxygen. Measurement of the PaO2 requires an arterial blood puncture, which is not routinely done on the ER or hospital ward. Therefore, the investigators will use an alternative method to determine the respiratory SOFA by determining the SpO2/FiO2 (SF) ratio, wherein SpO2 is peripheral oxygen saturation. SpO2 is routinely measured by finger pulse oximeter in patients with suspected infection; FiO2 is 21% when breathing room temperature and increases by 4% with each liter of oxygen provided per minute to a patient via a nasal cannula. Cut-off values for SF ratios correlating with SOFA pulmonary scores based on PF ratios have been validated in large data sets.

• Study Type: Observational
• Enrollment (Estimated): 3300

Contacts and Locations

• Study Contact: Name: Oren Turgman, MD, MsC; Phone Number: 0205669111; Email: biosep@amsterdamumc.nl
• Study Contact Backup: Name: Evelien Reijnders, MD, MsC; Phone Number: 0205669111; Email: biosep@amsterdamumc.nl

Study Locations

• Netherlands
  • Flevoland
    • Almere, Flevoland, Netherlands, 1315RA
      • Not yet recruiting
      • Flevoziekenhuis
      • Contact: Renee Douma, MD, PhD; Phone Number: 0368688888; Email: biosep@amsterdamumc.nl
  • North-Holland
    • Amsterdam, North-Holland, Netherlands, 1081HZ
      • Recruiting
      • Amsterdam Umc, Location Vumc
      • Contact: Prabath Nanayakkara, MD, PhD; Phone Number: 0204444444; Email: biosep@amsterdamumc.nl
    • Amsterdam, North-Holland, Netherlands, 1105AZ
      • Recruiting
      • Amsterdam UMC, location AMC
      • Contact: Willem Joost Wiersinga, MD, PhD; Phone Number: 0205669111; Email: biosep@amsterdamumc.nl

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

The research population will include adult patients that present to the ED of participating hospitals. In order to be eligible to participate in the BIOSEP study there must also be a clinical suspicion of an infection or a confirmed infection and MEWS of 2 or higher.

Description

Inclusion Criteria:

• Age 18 years or higher
• Presentation at the Emergency Department (ED)
• Clinical suspicion of infection or earlier confirmed infection
• Modified Early Warning Score (MEWS) of 2 or higher

Exclusion Criteria:

• No informed consent given

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with infection; Patients with an (suspected) infection and a MEWS score 2 or higher	Other: No intervention; There is no intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Final diagnosis for hospitalization	Adjudicated diagnoses for hospitalization	4 years
Disease severity	Sequential Organ Failure Assesment (SOFA) score (minimum 0, maximum 24) collected during admission	During hospitalization (up to day 180)
Mortality	Mortality at day 30	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of stay	Both hospital and ICU stay	During hospitalization (up to day 180)
Mortality	Hospital, ICU, 28-day, 90-day and 1 year mortality	5 years
Post-sepsis sequelae	Up to 1 year post sepsis, e.g. decreased executive functions, weakness, fatigue etc.)	Up to 1 year after sepsis episode
Readmissions	All cause readmissions in the first year after discharge	5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Site of infection	Site of infection	4 years
Initiated therapies during admission	Initiated therapies during admission	4 years

Collaborators and Investigators

• Sponsor: Amsterdam University Medical Centers (UMC), Location Academic Medical Center (AMC)
• Collaborators: Amsterdam UMC, location VUmc; Flevoziekenhuis
• Investigators: Principal Investigator: Willem Joost Wiersinga, MD, PhD, Amsterdam UMC, location AMC

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2022
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: November 23, 2023
• First Submitted That Met QC Criteria: December 11, 2023
• First Posted (Estimated): December 21, 2023

Study Record Updates

• Last Update Posted (Estimated): December 21, 2023
• Last Update Submitted That Met QC Criteria: December 11, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Biomarkers; Emergency Room; A&E; Accident & Emergency
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Disease Attributes; Bacterial Infections and Mycoses; Sepsis; Toxemia; Emergencies; Infections; Communicable Diseases; Virus Diseases; Respiratory Tract Infections; Bacterial Infections
• Other Study ID Numbers: BIOSEP

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