Inflammatory Markers in Trauma Patient Outcomes

NCT03671746 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 43611
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Polytrauma

Keywords

Inflammatory cytokine; inflammation; trauma; opioid

Outcome Measures

Primary Outcomes (1)

• Length of Hospital Stay

  Duration of the hospital stay will be calculated from electronic health record

  Up to 30 days

Secondary Outcomes (11)

• Morphine Milligram Equivalents in House

  Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5

• Change in Patient Pain Scores

  Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5

• Change in Interleukin 1a

  Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5

• Change in Interleukin 1b

  Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5

• Change in Interleukin 6

  Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5

Study Arms (2)

Standard of Care without NSAID

PLACEBO COMPARATOR

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

Standard of Care with NSAID

EXPERIMENTAL

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

Interventions

Ketorolac DRUG

Participants will receive Ketorolac at 15 mg IV every 6 hours for their first 5 days of hospitalization

Also known as: Toradol

Standard of Care with NSAID

Saline Solution DRUG

Participants will receive 1 ml of saline solution IV every 6 hours for their first 5 days of hospitalization

Also known as: Normal Saline

Standard of Care without NSAID

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Arun Aneja: lead

Study Sites (1)

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

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Related Links

• Pilot Study Results #1
• Pilot Study Results #2

MeSH Terms

Conditions

Multiple Trauma; Inflammation; Wounds and Injuries

Interventions

Ketorolac; Ketorolac Tromethamine; Saline Solution

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Indomethacin; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Limitations and Caveats

The study was unable to achieve the target enrollment of 56 patients per group due to the institution suspending all clinical trial enrollment during the COVID-19 pandemic. Blood samples were not able to be collected from two patients and clinical outcomes for one patient. Due to a transition in the institution's electronic medical record that occurred in 2021, one patient's chart could not be recovered, hence clinical outcomes could not be collected for this patient.

Results Point of Contact

• Title: Dr. Arun Aneja, MD, PhD
• Organization: Massachusetts General Hospital

aaneja@mgh.harvard.edu

617-726-6546

Study Officials

• Arun Aneja, MD

  University of Kentucky

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Participant medical team will be blinded to the treatment or placebo intervention
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Orthopaedic Surgery Traumatology Division

Model Details: Compare the effectiveness of a NSAID to placebo in acute trauma setting.

Study Record Dates

• First Submitted: September 12, 2018
• First Posted: September 14, 2018
• Study Start: February 28, 2019
• Primary Completion: June 20, 2023
• Study Completion: June 20, 2023
• Last Updated: June 5, 2025
• Results First Posted: June 5, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)