Inflammatory Markers in Trauma Patient Outcomes

June 4, 2025 updated by: Arun Aneja

Inflammatory Response to Trauma - Does Early Cytokine Modulation Improve Patient Outcome

It is unknown whether early modulation of inflammatory cytokines is associated with improved patient outcomes, reduced narcotic requirements in orthopaedic patient population, and improved patient subjective pain after hospital discharge. Preliminary animal and clinical studies have shown correlation between elevated blood cytokine concentrations during the acute phase of trauma and the development of post-traumatic complications. Early administration of nonsteroidal anti-inflammatory drug (NSAID) in animals significantly reduced inflammatory profiles, improved pulmonary edema, and enhanced arteriole vasoconstriction in response to hemorrhage. The ability to modify post-traumatic physiologic response via short-term administration of a non-steroidal anti-inflammatory drug (NSAID) may lead to improved patient outcome. In addition, given the current landscape for opioid epidemic in the United States, alternative non-opioid pain management during acute trauma has the potential to reduce opioid consumption and represents a pivotal component of multimodal analgesia strategy.

By doing this study, the investigators hope to learn how to provide the best care for all patients in the state of Kentucky. Patient participation in this research will last about 1 year.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Accidental trauma is the 4th leading cause of death in the United States, and it is associated with a complex inflammatory response. This response is associated with post-traumatic complications such as; multi-organ dysfunction syndrome (MODS), bacterial pneumonia, acute respiratory distress syndrome (ARDS), systemic inflammatory response syndrome (SIRS), and post-traumatic pain (PTP). It is unknown whether early modulation of inflammatory cytokines is associated with improved patient outcomes, reduced narcotic requirements, and improved patient subjective pain after hospital discharge.

Preliminary data has shown: (1) elevated blood cytokine concentrations during the acute phase of trauma are correlated with the development of fatal post-traumatic complications, (2) that early administration of a non-steroidal anti-inflammatory drug (NSAID) resulted in decreased blood serum levels of interleukin (IL-6), Prostaglandin E2 (PGE2), improved pulmonary edema, and enhanced arterioles ability to vasoconstrict in response to hemorrhage in animal models, and (3) that the addition of the internal physiologic parameters (inflammatory cytokines) to New Injury Severity Score (NISS - a marker of the external anatomical insult) significantly improves the ability to predict hospital length of stay of trauma patients when compared to NISS alone. The investigator's group is the first to use an integrative approach that combines the external anatomic injury data with the internal physiologic response for accurate prediction of a patient's clinical outcome. Therefore, if the investigators apply this same mindset to treatment, the investigators can improve the trauma patients' care by addressing both parameters as opposed to solely focusing on the external injury as done in the past. The ability to modify post-traumatic physiologic response via short-term administration of an NSAID may lead to improved patient outcomes.

Over the last decade, clinicians have remained puzzled over the safety of NSAID administration after fracture in terms of bone union. In addition, given the current landscape for the opioid epidemic in the United States, alternative non-opioid pain management during acute trauma has the potential to reduce opioid consumption and represents a pivotal component of multimodal analgesia strategy.

Study Type

Interventional

Enrollment (Actual)

70

Phase

  • Phase 1

Contacts and Locations

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

Study Locations

  • United States
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • University Of Kentucky

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

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients age 18 to 75
  • New Injury Severity Score (NISS) > 9, with musculoskeletal injury requiring surgical treatment

Exclusion Criteria:

  • Patient age < 18 or > 75
  • Patients who presented more than 24 hours after time of injury
  • Patients with contraindications to NSAID therapy (i.e., patients with active hemorrhage, received blood products, traumatic brain injury (TBI), active gastrointestinal bleeding or ulceration, NSAID allergy, thromboembolism, or coagulopathy)
  • Patients with pre-existing inflammatory condition (e.g., inflammatory arthropathy or bowel disease)
  • Patients with preexisting immunocompromised/immunosuppressed condition or acquired immunodeficiency syndrome (AIDS)
  • Patients with pre-existing comorbidities (e.g., coronary artery disease, myocardial infarction, chronic organ failure, chronic obstructive pulmonary disease, emphysema, asthma, etc.)
  • Patients with chronic use of steroids, immuno-modulating drugs, or history of organ transplantation
  • Patients receiving chronic opioid therapy or treatment for opioid use disorder
  • Patients who are pregnant
  • Patients with thermal injury

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

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Standard of Care without NSAID
Polytrauma participants will receive standard of care in addition to saline solution according to standard Advanced Trauma Life Support (ATLS) and standard ICU routine medical care.
Drug: Saline Solution
Participants will receive 1 ml of saline solution IV every 6 hours for their first 5 days of hospitalization
Other Names:
  • Normal Saline
Experimental: Standard of Care with NSAID
Participants in the group will receive Ketorolac in addition to standard of care for the standard Advanced Trauma Life Support (ATLS) and standard ICU routine medical care.
Drug: Ketorolac
Participants will receive Ketorolac at 15 mg IV every 6 hours for their first 5 days of hospitalization
Other Names:
  • Toradol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Length of Hospital Stay
Time Frame: Up to 30 days
Duration of the hospital stay will be calculated from electronic health record
Up to 30 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mortality
Time Frame: Up to 30 days
The Incidence of death related to the initial trauma/traumatic complications will be recorded for the first 30 days.
Up to 30 days
Morphine Milligram Equivalents in House
Time Frame: Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5
The the morphine milligram equivalents (MME) will be recorded throughout the course of the hospital stay. These will be reported as daily totals.
Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5
Change in Patient Pain Scores
Time Frame: Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5
The patient reported pain scores (visual analogue pain scores) will be recorded throughout the course of the hospital stay. The scores are reported by the patients and range from 0 indicating no pain to 100 meaning the worst pain imaginable. These will be reported as daily averages.
Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5
Change in Interleukin 1a
Time Frame: Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5
Daily blood collections during the first 5 days of hospitalization. Interleukin 1a will be measured by the sandwich ELISA, and data will be presented as change in the baseline level of Interleukin 1 from presentation to the emergency room to day 5 of hospitalization.
Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5
Change in Interleukin 1b
Time Frame: Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5
Daily blood collections during the first 5 days of hospitalization. Interleukin 1b will be measured by the sandwich ELISA, and data will be presented as change in the baseline level of Interleukin 1 from presentation to the emergency room to day 5 of hospitalization.
Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5
Change in Interleukin 6
Time Frame: Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5
Daily blood collections during the first 5 days of hospitalization. Interleukin 6 will be measured by the sandwich ELISA, and data will be presented as change in the baseline level of Interleukin 6 from presentation to the emergency room to day 5 of hospitalization.
Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5
Change in Interleukin 10
Time Frame: Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5
Daily blood collections during the first 5 days of hospitalization. Interleukin 10 will be measured by the sandwich ELISA, and data will be presented as change in the baseline level of Interleukin 10 from presentation to the emergency room to day 5 of hospitalization.
Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5
Change in Prostaglandin E-2
Time Frame: Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5
Blood will be collected over the course of 5 days of hospitalization. Prostaglandin E-2 will be measured by the sandwich ELISA, and data will be presented as change in the baseline level of Prostaglandin E-2 from presentation to the emergency room to day 5 of hospitalization
Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5
Post Traumatic Complications
Time Frame: Up to 30 days
The Incidence of post-traumatic complications in the patients which includes, but is not limited to the occurrence of pulmonary complications (i.e., bacterial pneumonia, pulmonary edema, acute respiratory failure) and AKI will be recorded throughout the duration of the hospital stay, usually up to 30 days. Data will be presented as the percentage of participants with a diagnosed post-traumatic complication.
Up to 30 days
Change in Inpatient Subjective Pain Reports
Time Frame: Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5
The patient reported pain scores (visual analogue pain scores) will be recorded throughout the course of the hospital stay. The scores are reported by the patients and range from 0 indicating no pain to 100 meaning the worst pain imaginable. These will be reported as daily averages.
Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5
Change in Outpatient Subjective Pain Reports
Time Frame: up to 365 days
Patient reports of level of pain and how much it inhibits their daily activities will be recorded in the outpatient setting. The scores are reported by the patients (visual analogue scale) and range from 0 indicating no pain to 100 meaning the worst pain imaginable. This will be reported for each patient follow-up visit. Several visits are possible and data will only be collected for the first year of follow-up. Data presented as the change in subject pain from baseline to 365 days.
up to 365 days

Collaborators and Investigators

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

Sponsor

Arun Aneja

Investigators

  • Principal Investigator: Arun Aneja, MD, University Of Kentucky

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

Helpful Links

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)

February 28, 2019

Primary Completion (Actual)

June 20, 2023

Study Completion (Actual)

June 20, 2023

Study Registration Dates

First Submitted

September 12, 2018

First Submitted That Met QC Criteria

September 13, 2018

First Posted (Actual)

September 14, 2018

Study Record Updates

Last Update Posted (Estimated)

June 5, 2025

Last Update Submitted That Met QC Criteria

June 4, 2025

Last Verified

June 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 43611

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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