New Strategy to Predict Early Sepsis

Development of a New Strategy to Predict Early Sepsis

This is an observational prospective multicentre study on patients attending the emergency department and suspected to have sepsis. Blood markers characteristic of a Cellular Reprogramming (CR) signature and predicting severe sepsis and organ failure will be measured and validated.

Study Overview

• Status: Active, not recruiting
• Conditions: Sepsis
• Intervention / Treatment: Other: Blood sample collection

Detailed Description

Sepsis is a life-threatening medical condition caused by an infection and the complex and dysfunctional way by which the human body attempts to deal with it. It can affect people of all ages, causing 18-30 million cases and 5-8 million deaths annually worldwide. However, early diagnosis of sepsis is challenging due to the diversity and overlap of symptoms with other disorders and the lack of an early and accurate diagnostic method. Hancock and colleagues defined a gene expression signature characteristic of biological changes occurring during sepsis, known as cellular reprogramming (CR) and reflecting a type of immune amnesia (inability to respond to bacterial signals). This signature was shown to predict the development of sepsis and organ failure at first clinical presentation in the emergency room, by examining patient blood samples taken during an initial pilot single-center study.

This project will validate and refine the CR signature and demonstrate reproducibility, specificity, and sensitivity in a larger multi-center study to enable a new strategy to predict Sepsis.

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Susan Farmer, BSc; Phone Number: 604-827-5663; Email: sfarmer@mail.ubc.ca

Study Locations

• Australia
  • Sydney, Australia
    • Westmead Hospital
• Canada
  • Vancouver, Canada
    • Vancouver General Hospital
• Colombia
  • Neiva, Colombia
    • Hospital Universitario Moncaleano Perdomo
• Netherlands
  • Groningen, Netherlands
    • University Medical Center Groningen
• United States
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas, M.D. Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients suspected of sepsis will be recruited at the emergency department of participating institutions.

Description

Inclusion Criteria:

• Male or female
• Presenting to the Emergency Department
• Attending physician suspects possible sepsis based on at least 2 sign of Systemic inflammatory response syndrome (SIRS) criteria and suspicion of infection

Exclusion Criteria:

• Patient is terminal (death anticipated in 12 hours)
• Informed consent unobtainable if the subject survives to hospital discharge.
• Subjects who are unable to provide blood as a standard of care.
• Blood sample could not be taken within 24 hours of a physician's first contact with the patient.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Suspected Sepsis Group; Participants suspected of potential to develop sepsis recruited at the emergency department.	Other: Blood sample collection; A blood sample (1 tube) will be collected for the analysis of the CR signature.
Surgical Group; Participants undergoing non-emergency scheduled surgery, including ear/nose and throat cases, orthopaedic surgery of the major joints including hip, knee, ankle, shoulder, and wrist.	Other: Blood sample collection; A blood sample (1 tube) will be collected for the analysis of the CR signature.
Healthy Group; Healthy participants	Other: Blood sample collection; A blood sample (1 tube) will be collected for the analysis of the CR signature.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of illness	Measured by serial Sequential Organ Failure Assessment (SOFA) score monitoring	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sequential Organ Failure Assessment (SOFA) Score monitoring	The organs scored are respiratory, cardiovascular, neurologic, hematologic, renal, and liver. Each organ is scored as 0 (best) to 4 (worse) and the total score is the sum of each component.	72 hours
Mortality	28-day survival rate after admission to hospital	28 days
ICU length of stay	Length of stay in the Intensive Care Unit	28 days
Quick Sequential Organ Failure Assessment (SOFA) Score greater than 2	Measured by serial Sequential Organ Failure Assessment (SOFA) score monitoring	6 hours

Collaborators and Investigators

• Sponsor: University of British Columbia
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Robert E Hancock, PhD, University of British Columbia

Publications and helpful links

General Publications

• Pena OM, Hancock DG, Lyle NH, Linder A, Russell JA, Xia J, Fjell CD, Boyd JH, Hancock RE. An Endotoxin Tolerance Signature Predicts Sepsis and Organ Dysfunction at Initial Clinical Presentation. EBioMedicine. 2014 Nov 1;1(1):64-71. doi: 10.1016/j.ebiom.2014.10.003.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2018
• Primary Completion (Estimated): July 31, 2023
• Study Completion (Estimated): July 31, 2023

Study Registration Dates

• First Submitted: October 4, 2019
• First Submitted That Met QC Criteria: October 4, 2019
• First Posted (Actual): October 8, 2019

Study Record Updates

• Last Update Posted (Actual): June 5, 2023
• Last Update Submitted That Met QC Criteria: June 2, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia
• Other Study ID Numbers: H17-01208

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The RNA-Seq data will be uploaded to Geo database when the study is complete or upon publication and will be freely available to researchers.

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