Inflammatory Markers in Trauma Patient Outcomes

Polytrauma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03671746
• Other study ID #: 43611
• Status: Completed
• Phase: Phase 1
• Start date: February 28, 2019
• Est. completion date: June 20, 2023

Study information

• Verified date: September 2023
• Source: University of Kentucky
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 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 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 a NSAID may lead to improved patient outcome.

Over the last decade, clinicians remain puzzled over the safety of NSAID administration after fracture in terms of bone union. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: June 20, 2023
• Est. primary completion date: June 20, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

-

Exclusion Criteria:

• Patient age < 18 or > 65

• Patients with injury more than 24 hours prior to evaluation

• Hemorrhagic shock or risk of significant hemorrhage.

• Patients with preexisting inflammatory medical condition such as inflammatory arthropathy or inflammatory bowel disease

• Patients with acquired immunodeficiency syndrome (AIDS)

• Patients who are pregnant

• Patients with active GI bleed or ulceration

• Patients with chronic use of steroids or immune modulating drugs or history of organ transplantation

• Patients with preexisting chronic renal, liver, or lung disease

• Patients with history of myocardial infarctions

• Patients with chronic heart failure

• Patients with allergy to NSAID

• Patients with coagulation defects (Clotting factor deficiencies, thrombophilia, or any bleeding disorder)

• Patients receiving chronic opioid therapy or treatment for opioid use disorder.

Related Conditions & MeSH terms

• Multiple Trauma
• Polytrauma

Intervention

Drug:
• Ketorolac
Participants will receive Ketorolac at 30 mg IV every 6 hours for their first 5 days of hospitalization
• Saline Solution
Participants will receive 10 ml of saline solution IV every 6 hours for their first 5 days of hospitalization

Locations

Country	Name	City	State
United States	University of Kentucky	Lexington	Kentucky

Sponsors (1)

Lead Sponsor	Collaborator
Arun Aneja

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Length of Hospital Stay	Duration of the hospital stay will be calculated from electronic health record	Up to 30 days
Secondary	Change in Interleukin 1	Daily blood collections during the first 5 days of hospitalization. Interleukin 1 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.	baseline and day 1, 2, 3 ,4 and 5
Secondary	Change in Interleukin 6	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.	baseline and day 1, 2, 3 ,4 and 5
Secondary	Change in Interleukin 10	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.	baseline and day 1, 2, 3 ,4 and 5
Secondary	Change in Prostaglandin E-2	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	baseline and day 1, 2, 3 ,4 and 5
Secondary	Post Traumatic Complications	The Incidence of post traumatic complications in the patients which includes, but is not limited to the occurrence of SIRS, MODS, bacterial pneumonia, and ARDS will be recorded throughout the duration of the hospital stay, usually up to 30 days. Data will be presented as the percent of participants with a diagnosed post traumatic complication of any kind.	Up to 30 days
Secondary	Mortality	The Incidence of death related to the initial trauma/traumatic complications will be recorded for the first 30 days.	Up to 30 days
Secondary	Change in Patient Pain Scores	The patient reported pain scores (visual analog 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 10 meaning the worst pain imaginable. These will be reported as daily averages.	Up to 30 days
Secondary	Morphine Milligram Equivalents in House	The the morphine milligram equivalents (MME) will be recorded throughout the course of the hospital stay. These will be reported as daily totals.	Up to 30 days
Secondary	Change in Inpatient Subjective Pain Reports	This will be in the form of patient response. If patient reports severe levels of pain this will be documented accordingly. Data will be collected periodically during hospitalization which typically lasts less than 30 days.	up to 30 days
Secondary	Change in Outpatient Subjective Pain Reports	Patients reports of level of pain and how much it inhibits their daily activities will be recorded in the outpatient setting. 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 will be presented as the change in subject pain over time (up to 356 days)	up to 365 days