The Usefulness of Inflammatory Markers to Predict Poor Outcomes for Trauma Patients

August 4, 2023 updated by: Kwangmin Kim, Wonju Severance Christian Hospital

Comparison of Inflammatory Markers (Serum Mitochondrial DNA, Delta Neutrophil Index, Inflammatory Cytokines) According to the Injury Severity, and Development of Risk Prediction Model Using Inflammatory Markers for Trauma Patients

1) Research Hypothesis

  1. Trauma -> Inflammation -> Severe inflammation -> Poor prognosis
  2. If the degree of inflammation in the serum is precisely measurable, the prognosis of patients with trauma can be predicted. In addition, if inflammatory processes linked to serum mitochondrial DNA copy number (smtDNAcn) and delta neutrophil index (DNI) are demonstrated, early intervention to improve outcomes in patients with trauma and a poor prognosis may be possible.

2) Basis of Research Hypothesis

  1. The Sequential Organ Failure Assessment (SOFA) score is currently used as a measurement tool to evaluate the severity and prognosis of critically ill patients. Recently, some studies reported that the DNI, an inflammatory index, is useful as a prognostic index. Although DNI is a simple prognostic index, further studies are necessary to investigate its usefulness as a reliable prognostic index for severely injured patients.

  2. Therefore, this study aimed to:

    i. prospectively analyze the effectiveness of DNI by measuring the degree of inflammation in severely injured patients;

    ii. Measure serum mitochondrial DNA, which is suggested as a mechanism preceding DNI elevation, and identify the sequence of inflammatory steps leading to circulating mitochondrial DNA as a damage-associated molecular pattern (DAMP), DNI, neutrophils, and inflammatory cytokines; and

    iii. Establish the effectiveness of each indicator as a prognostic factor, construct a prediction model for poor prognosis, and prove the effectiveness of the final risk model.

Study Overview

Status

Recruiting

Conditions

Detailed Description

1) Research Objectives

  1. Quantitative measurement of serum mtDNA copy number (smtDNAcn), delta neutrophil index (DNI), and inflammatory cytokines [interleukin (IL) -1β/2/6/12, Interferon (IFN-ℽ), Tumor necrosis factor (TNF-α), IL-4/10)] over time
  2. Analysis of correlation between smtDNAcn, DNI, and inflammatory cytokines (IL-1β/2/6/12, IFN-ℽ, TNF-α, IL-4/10) at initial presentation, on trauma days #1 and #2, and poor outcomes [multiorgan distress syndrome (MODS), mortality]
  3. Construction and validation of a prognostic index using biological markers associated with inflammation (smtDNAcn, DNI, and inflammatory cytokines)

2) Contents of the Research Project

  1. Measurement of biological indicators over time - Measurement of smtDNAcn, DNI, and inflammatory cytokines over time using polymerase chain reaction (PCR) and multiplex assay in patients classified as severely injured based on the injury severity score (ISS) (ISS ≥16).
  2. Analysis of correlation between biologic markers and poor outcomes (MODS, mortality) - Identification of independent risk factors to predict poor outcomes such as MODS and mortality among inflammatory markers (serum mtDNA copy number, DNI, neutrophil count, and inflammatory cytokines) in this study.
  3. Predictive Model Construction and Validation - Construction of a scoring system using inflammatory markers (smtDNAcn, DNI, neutrophils, and cytokines) and comparison with the SOFA score

3) Strategies and methods for the research project

  1. A. Subjects: all trauma patients who visited Wonju Severance Christian hospital, regional trauma center.

  2. Study period and patients recruitment

    i. 1st and 2nd year (until construction of prognostic scoring system): 200 patients (MODS:50, mortality: 50)

    ii. 3rd year (for validation): 100 patients (MODS: 30, mortality: 30)

  3. Measurement of serum mtDNA copy number, DNI, and inflammatory cytokines

    i. Blood sampling: At the initial presentation and again on trauma days #1 and #2.

    ii. smtDNAcn, cytokines (IL-1β/2/6/12, IFN-ℽ, TNF-α, IL-4/10) by PCR, multiplex, and DNI using an automatic cell analyzer.

  4. Analysis of correlation between biologic markers and poor outcomes (MODS, mortality)

    i. Statistical analysis of inflammatory markers such as smtDNAcn, cytokines (IL-1β/2/6/12, IFN-ℽ, TNF-α, IL-4/10) measured at the initial presentation, on trauma day #1, and #2 between severely injured patients with no poor outcomes and those with poor outcomes such as MODS and mortality risk.

  5. Risk model construction using inflammatory markers to predict MODS and mortality risk

    i. Recruitment of 100 severely injured patients for validation on 3rd year during study period

    ii. The recruited patients were divided into low-risk and high-risk groups according to the new risk model, cut-off value of each inflammatory marker, and SOFA score.

    iii. Comparison of sensitivity and specificity of the new risk model, inflammatory markers, and SOFA score.

Study Type

Observational

Enrollment (Estimated)

300

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

All severely injured patients with injury severiry score ≥ 16 older than 19 years of age who visited Wonju Severance Christian Hospital, regional trauma center will be included in the study

Description

Inclusion Criteria:

  • Injury severity score ≥ 16

Exclusion Criteria:

  • Age ≤18 years
  • Pregnancy in women
  • Death at initial presentation of the case
  • Patients who refused to participate in the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mortality (dichotomous)
Time Frame: Within 30 days after trauma
The number of deaths
Within 30 days after trauma
Multiorgan distress syndrome (dichotomous)
Time Frame: Within 30 days after trauma
The number of patients with SOFA ≥ 6
Within 30 days after trauma

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hospital length of stay (continuous)
Time Frame: From date of the admission until the date of first discharge from the hospital, assessed up to 60 days
Measured in days from admission to discharge
From date of the admission until the date of first discharge from the hospital, assessed up to 60 days
Intensive care unit (ICU) stay (continuous)
Time Frame: From date of ICU admission (in cases of ICU admission at the initial presentation) until the date of first discharge from ICU, assessed up to 60 days
Measured in days from ICU admission to ICU out
From date of ICU admission (in cases of ICU admission at the initial presentation) until the date of first discharge from ICU, assessed up to 60 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Wonju Severance Christian Hospital

Collaborators

National Research Foundation of Korea

Investigators

  • Principal Investigator: Kwangmin Kim, Yonsei University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 25, 2022

Primary Completion (Estimated)

May 31, 2024

Study Completion (Estimated)

May 31, 2025

Study Registration Dates

First Submitted

June 23, 2022

First Submitted That Met QC Criteria

June 28, 2022

First Posted (Actual)

July 1, 2022

Study Record Updates

Last Update Posted (Actual)

August 7, 2023

Last Update Submitted That Met QC Criteria

August 4, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PMT2022
  • 2022R1I1A1A01068599 (Other Grant/Funding Number: National Research Foundation of Korea)

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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