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

NCT ID: NCT05441787

Last Updated: 2024-06-11

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 89 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-07-25
• Study Completion Date: 2024-06-10

Brief Summary

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.

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.

Conditions

Trauma Injury; Trauma, Multiple

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

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

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Research Foundation of Korea

OTHER

Sponsor Role: collaborator

Wonju Severance Christian Hospital

OTHER

Sponsor Role: lead

Responsible Party

Kwangmin Kim

Clinical assistant professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kwangmin Kim

Role: PRINCIPAL_INVESTIGATOR

Yonsei University

Locations

Wonju Severance Christian Hospital

Wŏnju, Gangwon-do, South Korea

Countries

South Korea

References

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Other Identifiers

2022R1I1A1A01068599

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

PMT2022

Identifier Type: -

Identifier Source: org_study_id