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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ketorolac | Drug | Participants will receive Ketorolac at 15 mg IV every 6 hours for their first 5 days of hospitalization |
|
| Measure | Description | Time Frame |
|---|---|---|
| Length of Hospital Stay | Duration of the hospital stay will be calculated from electronic health record | Up to 30 days |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5 |
| Change in Patient Pain Scores |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Arun Aneja, MD | University of Kentucky | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Kentucky | Lexington | Kentucky | 40536 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18676205 | Background | Braden JB, Fan MY, Edlund MJ, Martin BC, DeVries A, Sullivan MD. Trends in use of opioids by noncancer pain type 2000-2005 among Arkansas Medicaid and HealthCore enrollees: results from the TROUP study. J Pain. 2008 Nov;9(11):1026-35. doi: 10.1016/j.jpain.2008.06.002. Epub 2008 Jul 26. | |
| 32584407 | Background |
| Label | URL |
|---|---|
| Pilot Study Results #1 | View source |
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No enrolled participants were excluded from the study before assignment to groups.
After obtaining institutional review board approval at a single Level I trauma center and clinical trial registration (ClinicalTrials.gov; NCT03671746), potential subjects were screened, recruited, and enrolled from February 2019 to October 2022. The types of locations in which participants were enrolled included the institution's emergency department, pre-operative holding area, or hospital unit.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. Saline Solution: Participants will receive 1 ml of saline solution IV every 6 hours for their first 5 days of hospitalization |
| FG001 | 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) or ICU routine medical care. Ketorolac: Participants will receive Ketorolac at 15 mg IV every 6 hours for their first 5 days of hospitalization |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Standard of Care Without NSAID | Polytrauma participants will receive standard of care in addition to saline solution according to standard ATLS and standard ICU routine medical care. Saline Solution: Participants will receive 1 ml of saline solution IV every 6 hours for their first 5 days of hospitalization |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Length of Hospital Stay | Duration of the hospital stay will be calculated from electronic health record | Posted | Median | Inter-Quartile Range | days | Up to 30 days |
|
Up to 30 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Standard of Care Without NSAID | Polytrauma participants will receive standard of care in addition to saline solution according to standard ATLS and standard ICU routine medical care. Saline Solution: Participants will receive 1 ml of saline solution IV every 6 hours for their first 5 days of hospitalization |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pulmonary Complications | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Pulmonary complications were defined as bacterial pneumonia, pulmonary edema, or acute respiratory failure. |
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Arun Aneja, MD, PhD | Massachusetts General Hospital | 617-726-6546 | aaneja@mgh.harvard.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 22, 2023 | Apr 10, 2024 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Oct 10, 2022 | Apr 10, 2024 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D009104 | Multiple Trauma |
| D007249 | Inflammation |
| D014947 | Wounds and Injuries |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D020910 | Ketorolac |
| D020911 | Ketorolac Tromethamine |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D007213 | Indomethacin |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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Compare the effectiveness of a NSAID to placebo in acute trauma setting.
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Participant medical team will be blinded to the treatment or placebo intervention
| Saline Solution | Drug | Participants will receive 1 ml of saline solution IV every 6 hours for their first 5 days of hospitalization |
|
|
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 | 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 | 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 | 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 | 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 | 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 | 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 |
| Mortality | The Incidence of death related to the initial trauma/traumatic complications will be recorded for the first 30 days. | Up to 30 days |
| Change in Inpatient Subjective Pain Reports | 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 | 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 |
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| 23159957 | Background | Sikka G, Miller KL, Steppan J, Pandey D, Jung SM, Fraser CD 3rd, Ellis C, Ross D, Vandegaer K, Bedja D, Gabrielson K, Walston JD, Berkowitz DE, Barouch LA. Interleukin 10 knockout frail mice develop cardiac and vascular dysfunction with increased age. Exp Gerontol. 2013 Feb;48(2):128-35. doi: 10.1016/j.exger.2012.11.001. Epub 2012 Nov 13. |
| 28526155 | Background | Vadivelu N, Chang D, Helander EM, Bordelon GJ, Kai A, Kaye AD, Hsu D, Bang D, Julka I. Ketorolac, Oxymorphone, Tapentadol, and Tramadol: A Comprehensive Review. Anesthesiol Clin. 2017 Jun;35(2):e1-e20. doi: 10.1016/j.anclin.2017.01.001. Epub 2017 Apr 14. |
| 29601492 | Background | Rogero MM, Calder PC. Obesity, Inflammation, Toll-Like Receptor 4 and Fatty Acids. Nutrients. 2018 Mar 30;10(4):432. doi: 10.3390/nu10040432. |
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| 23395471 | Background | Mazzocca AD, McCarthy MB, Intravia J, Beitzel K, Apostolakos J, Cote MP, Bradley J, Arciero RA. An in vitro evaluation of the anti-inflammatory effects of platelet-rich plasma, ketorolac, and methylprednisolone. Arthroscopy. 2013 Apr;29(4):675-83. doi: 10.1016/j.arthro.2012.12.005. Epub 2013 Feb 6. |
| 35404445 | Background | Zhang W, Mei R, Wu S. Ketorolac tromethamine represses senescence in aging articular chondrocytes. Biosci Biotechnol Biochem. 2022 Jun 25;86(7):837-845. doi: 10.1093/bbb/zbac047. |
| 23218935 | Background | Carvalho B, Lemmens HJ, Ting V, Angst MS. Postoperative subcutaneous instillation of low-dose ketorolac but not hydromorphone reduces wound exudate concentrations of interleukin-6 and interleukin-10 and improves analgesia following cesarean delivery. J Pain. 2013 Jan;14(1):48-56. doi: 10.1016/j.jpain.2012.10.002. Epub 2012 Dec 4. |
| 11289091 | Background | Kim MH, Hahm TS. Plasma levels of interleukin-6 and interleukin-10 are affected by ketorolac as an adjunct to patient-controlled morphine after abdominal hysterectomy. Clin J Pain. 2001 Mar;17(1):72-7. doi: 10.1097/00002508-200103000-00010. |
| 26028838 | Background | Singh P, Rastogi S, Bansal M, Kumar S, Singh R, Nishad SG, Reddy MP, Anand KR, Kumar S, Thayath MN. A prospective study to assess the levels of interleukin-6 following administration of diclofenac, ketorolac and tramadol after surgical removal of lower third molars. J Maxillofac Oral Surg. 2015 Jun;14(2):219-25. doi: 10.1007/s12663-013-0609-1. Epub 2014 Feb 18. |
| 28468607 | Background | Kuchalik J, Magnuson A, Tina E, Gupta A. Does local infiltration analgesia reduce peri-operative inflammation following total hip arthroplasty? A randomized, double-blind study. BMC Anesthesiol. 2017 May 3;17(1):63. doi: 10.1186/s12871-017-0354-y. |
| 27546764 | Background | Namas RA, Almahmoud K, Mi Q, Ghuma A, Namas R, Zaaqoq A, Zhu X, Abdul-Malak O, Sperry J, Zamora R, Billiar TR, Vodovotz Y. Individual-specific principal component analysis of circulating inflammatory mediators predicts early organ dysfunction in trauma patients. J Crit Care. 2016 Dec;36:146-153. doi: 10.1016/j.jcrc.2016.07.002. Epub 2016 Jul 11. |
| 17652366 | Background | Levy RM, Mollen KP, Prince JM, Kaczorowski DJ, Vallabhaneni R, Liu S, Tracey KJ, Lotze MT, Hackam DJ, Fink MP, Vodovotz Y, Billiar TR. Systemic inflammation and remote organ injury following trauma require HMGB1. Am J Physiol Regul Integr Comp Physiol. 2007 Oct;293(4):R1538-44. doi: 10.1152/ajpregu.00272.2007. Epub 2007 Jul 25. |
| 19895952 | Background | Giannoudis PV, Giannoudi M, Stavlas P. Damage control orthopaedics: lessons learned. Injury. 2009 Nov;40 Suppl 4:S47-52. doi: 10.1016/j.injury.2009.10.036. |
| 37466669 | Background | Billiar TR, Hunt BJ, Bailly S. Targeting inflammation in traumatic injury: entering a new era. Intensive Care Med. 2023 Aug;49(8):977-978. doi: 10.1007/s00134-023-07152-2. Epub 2023 Jul 19. No abstract available. |
| 21483522 | Background | Namas R, Ghuma A, Hermus L, Zamora R, Okonkwo DO, Billiar TR, Vodovotz Y. The acute inflammatory response in trauma / hemorrhage and traumatic brain injury: current state and emerging prospects. Libyan J Med. 2009 Sep 1;4(3):97-103. doi: 10.4176/090325. |
| 26584270 | Background | Giannoudis PV, Hak D, Sanders D, Donohoe E, Tosounidis T, Bahney C. Inflammation, Bone Healing, and Anti-Inflammatory Drugs: An Update. J Orthop Trauma. 2015 Dec;29 Suppl 12:S6-9. doi: 10.1097/BOT.0000000000000465. |
| 20552333 | Background | Dodwell ER, Latorre JG, Parisini E, Zwettler E, Chandra D, Mulpuri K, Snyder B. NSAID exposure and risk of nonunion: a meta-analysis of case-control and cohort studies. Calcif Tissue Int. 2010 Sep;87(3):193-202. doi: 10.1007/s00223-010-9379-7. Epub 2010 Jun 15. |
| 37752630 | Result | Foster JA, Kavolus MW, Landy DC, Pectol RW, Sneed CR, Kinchelow DL, Griffin JT, Hawk GS, Bernard AC, Oyler DR, Aneja A. Low-Dose Short-Term Scheduled Ketorolac Reduces Opioid Use and Pain in Orthopaedic Polytrauma Patients: A Randomized Clinical Trial. J Orthop Trauma. 2023 Dec 1;37(12):633-639. doi: 10.1097/BOT.0000000000002703. |
| 38506517 | Result | Foster JA, Hawk GS, Landy DC, Griffin JT, Bernard AC, Oyler DR, Southall WGS, Muhammad M, Sierra-Arce CR, Mounce SD, Borgida JS, Xiang L, Aneja A. Does Scheduled Low-Dose Short-Term NSAID (Ketorolac) Modulate Cytokine Levels After Orthopaedic Polytrauma? A Secondary Analysis of a Randomized Clinical Trial. J Orthop Trauma. 2024 Jul 1;38(7):358-365. doi: 10.1097/BOT.0000000000002807. |
| Pilot Study Results #2 | View source |
| Standard of Care With NSAID |
Participants in the group will receive Ketorolac in addition to standard of care for the standard ATLS or ICU routine medical care. Ketorolac: Participants will receive Ketorolac at 15 mg IV every 6 hours for their first 5 days of hospitalization |
| BG002 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m^2 |
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| New Injury Severity Score (NISS) | The New Injury Severity Score (NISS) is a modification of the Injury Severity Score (ISS), which serves as a scale for determining injury burden in polytrauma patients. To calculate the NISS, the sum of squares of the three most severe injuries are calculated, regardless of body region. Each injury is scored from 0 to 3, with 3 being the most severe. Since the sum of squares of the three most severe injuries is calculated, this provides a NISS scale of 0 to 27, with 0 being no injury to 27 being the most severe injury burden. | Mean | Standard Deviation | units on a scale |
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| Surgery Count | Mean | Standard Deviation | number of surgeries |
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| 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. | Posted | Median | Inter-Quartile Range | morphine milligram equivalents | Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5 |
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| Secondary | Change in Patient Pain Scores | 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. | Posted | Mean | Standard Deviation | score on a scale | Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5 |
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| Secondary | Change in Interleukin 1a | 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. | The cytokine analysis was limited to only short-term inpatient data collected from the date of admission to inpatient Day 3. While research personnel attempted to recruit patients with anticipated hospital stays of at least five days, there was a notable decrease in hospitalized subjects past Day 3. To maintain study power and make meaningful conclusions, the authors decided to present findings analyzed during the first three hospital days. | Posted | Median | Inter-Quartile Range | fg/mL | Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5 |
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| Secondary | Change in Interleukin 1b | 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. | The cytokine analysis was limited to only short-term inpatient data collected from the date of admission to inpatient Day 3. While research personnel attempted to recruit patients with anticipated hospital stays of at least five days, there was a notable decrease in hospitalized subjects past Day 3. To maintain study power and make meaningful conclusions, the authors decided to present findings analyzed during the first three hospital days. | Posted | Median | Inter-Quartile Range | pg/mL | Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5 |
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| 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. | The cytokine analysis was limited to only short-term inpatient data collected from the date of admission to inpatient Day 3. While research personnel attempted to recruit patients with anticipated hospital stays of at least five days, there was a notable decrease in hospitalized subjects past Day 3. To maintain study power and make meaningful conclusions, the authors decided to present findings analyzed during the first three hospital days. | Posted | Median | Inter-Quartile Range | pg/mL | Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5 |
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| 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. | The cytokine analysis was limited to only short-term inpatient data collected from the date of admission to inpatient Day 3. While research personnel attempted to recruit patients with anticipated hospital stays of at least five days, there was a notable decrease in hospitalized subjects past Day 3. To maintain study power and make meaningful conclusions, the authors decided to present findings analyzed during the first three hospital days. | Posted | Median | Inter-Quartile Range | pg/mL | Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5 |
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| 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 | The cytokine analysis was limited to only short-term inpatient data collected from the date of admission to inpatient Day 3. While research personnel attempted to recruit patients with anticipated hospital stays of at least five days, there was a notable decrease in hospitalized subjects past Day 3. To maintain study power and make meaningful conclusions, the authors decided to present findings analyzed during the first three hospital days. | Posted | Median | Inter-Quartile Range | pg/mL | Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5 |
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| Secondary | Post Traumatic Complications | 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. | Two participants were excluded from the secondary analysis, as blood samples were not able to be collected from these patients. Due to a transition in our institution's electronic medical record, one patient's chart could not be recovered, hence secondary clinical outcomes could not be collected for this patient (n=67). | Posted | Count of Participants | Participants | Up to 30 days |
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| Secondary | Mortality | The Incidence of death related to the initial trauma/traumatic complications will be recorded for the first 30 days. | Two participants were excluded from the secondary analysis, as blood samples were not able to be collected from these patients (n=68). Due to a transition in our institution's electronic medical record, one patient's chart could not be recovered, hence secondary clinical outcomes could not be collected for this patient. | Posted | Count of Participants | Participants | Up to 30 days |
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| Secondary | Change in Inpatient Subjective Pain Reports | 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. | Change in patient pain scores during the hospital stay was inadvertently entered twice (as outcomes #3: Change in Patient Pain Scores and #11: Change in Inpatient Subjective Pain Reports). These represent identical outcomes which was change in patient pain during the hospital stay. Please refer to outcome #3 for the corresponding data. | Posted | Mean | Standard Deviation | score on a scale | Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5 |
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| Secondary | Change in Outpatient Subjective Pain Reports | 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. | Only nine patients completed the required follow-up, resulting in insufficient data to conduct meaningful statistical analysis or draw clinically relevant conclusions. | Posted | Mean | Full Range | units on a scale | up to 365 days |
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| 0 |
| 35 |
| 0 |
| 35 |
| 6 |
| 35 |
| EG001 | Standard of Care With NSAID | Participants in the group will receive Ketorolac in addition to standard of care for the standard ATLS or ICU routine medical care. Ketorolac: Participants will receive Ketorolac at 15 mg IV every 6 hours for their first 5 days of hospitalization | 0 | 35 | 0 | 35 | 3 | 35 |
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| Acute Kidney Injury | Renal and urinary disorders | Systematic Assessment | Acute kidney injury was defined as an increase in serum creatinine greater than or equal to 0.3 mg/dL within a 48-hour period. |
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Not provided
Not provided
| D006571 | Heterocyclic Compounds |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
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Group-level summary statistics were calculated for demographic and clinical variables, and differences between groups were evaluated using two-sample t-tests for quantitative measures and Fisher's exact tests for categorical measures, as appropriate. Time and group comparisons for each cytokine were made using linear mixed models, with and without adjusting for selected covariates. Patient demographic variables and clinical outcomes of interest were considered for inclusion as covariates in each model but were only retained if they significantly improved the model. Linear mixed models were log-transformed, double-log-transformed, or square-root-transformed to correct for right skewness, as appropriate. Likelihood ratio testing and Akaike information criterion were used to select appropriate covariance structures in each case. All analyses were completed in SAS 9.4 (SAS Institute Inc.; Cary, NC, USA). |
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Group-level summary statistics were calculated for demographic and clinical variables, and differences between groups were evaluated using two-sample t-tests for quantitative measures and Fisher's exact tests for categorical measures, as appropriate. Time and group comparisons for each cytokine were made using linear mixed models, with and without adjusting for selected covariates. Patient demographic variables and clinical outcomes of interest were considered for inclusion as covariates in each model but were only retained if they significantly improved the model. Linear mixed models were log-transformed, double-log-transformed, or square-root-transformed to correct for right skewness, as appropriate. Likelihood ratio testing and Akaike information criterion were used to select appropriate covariance structures in each case. All analyses were completed in SAS 9.4 (SAS Institute Inc.; Cary, NC, USA). |
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Group-level summary statistics were calculated for demographic and clinical variables, and differences between groups were evaluated using two-sample t-tests for quantitative measures and Fisher's exact tests for categorical measures, as appropriate. Time and group comparisons for each cytokine were made using linear mixed models, with and without adjusting for selected covariates. Patient demographic variables and clinical outcomes of interest were considered for inclusion as covariates in each model but were only retained if they significantly improved the model. Linear mixed models were log-transformed, double-log-transformed, or square-root-transformed to correct for right skewness, as appropriate. Likelihood ratio testing and Akaike information criterion were used to select appropriate covariance structures in each case. All analyses were completed in SAS 9.4 (SAS Institute Inc.; Cary, NC, USA). |
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Group-level summary statistics were calculated for demographic and clinical variables, and differences between groups were evaluated using two-sample t-tests for quantitative measures and Fisher's exact tests for categorical measures, as appropriate. Time and group comparisons for each cytokine were made using linear mixed models, with and without adjusting for selected covariates. Patient demographic variables and clinical outcomes of interest were considered for inclusion as covariates in each model but were only retained if they significantly improved the model. Linear mixed models were log-transformed, double-log-transformed, or square-root-transformed to correct for right skewness, as appropriate. Likelihood ratio testing and Akaike information criterion were used to select appropriate covariance structures in each case. All analyses were completed in SAS 9.4 (SAS Institute Inc.; Cary, NC, USA). |
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Group-level summary statistics were calculated for demographic and clinical variables, and differences between groups were evaluated using two-sample t-tests for quantitative measures and Fisher's exact tests for categorical measures, as appropriate. Time and group comparisons for each cytokine were made using linear mixed models, with and without adjusting for selected covariates. Patient demographic variables and clinical outcomes of interest were considered for inclusion as covariates in each model but were only retained if they significantly improved the model. Linear mixed models were log-transformed, double-log-transformed, or square-root-transformed to correct for right skewness, as appropriate. Likelihood ratio testing and Akaike information criterion were used to select appropriate covariance structures in each case. All analyses were completed in SAS 9.4 (SAS Institute Inc.; Cary, NC, USA). |
Group-level summary statistics were calculated for demographic and clinical variables, and differences between groups were evaluated using two-sample t-tests for quantitative measures and Fisher's exact tests for categorical measures, as appropriate. Time and group comparisons for each cytokine were made using linear mixed models, with and without adjusting for selected covariates. Patient demographic variables and clinical outcomes of interest were considered for inclusion as covariates in each model but were only retained if they significantly improved the model. Linear mixed models were log-transformed, double-log-transformed, or square-root-transformed to correct for right skewness, as appropriate. Likelihood ratio testing and Akaike information criterion were used to select appropriate covariance structures in each case. All analyses were completed in SAS 9.4 (SAS Institute Inc.; Cary, NC, USA). |
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