Danger Response in Polytrauma Patients (NTF-PT)

Analysis of the Danger Response After Polytrauma Based on the National Polytrauma-serum-bank of the Trauma Research Network (NTF) of the German Society for Orthopaedics and Trauma (DGOU)

The NTF_PT_2014 multicenter study aims to collect, store, and analyse plasma and serum from polytrauma-patients (injury severity score ≥25) and corresponding clinical data to address 1) how trauma modulates the release of danger molecules, inflammatory mediators, coagulation factors and novel biomarkers, 2) how the specific injury pattern affects the posttraumatic response and regenerative potential on an organ-, cell, and molecular level, and 3) how could a specific organ- and immune-monitoring predict the clinical outcome.

Study Overview

• Status: Unknown
• Conditions: Multiple Trauma
• Intervention / Treatment: Procedure: blood drawing

Detailed Description

Polytrauma is worldwide a major socio-economic problem. Especially the polytrauma-induced complications, such as systemic inflammatory response, sepsis, organ dysfunction remain associated with a high morbidity and mortality rate. The underlying posttraumatic pathophysiology remains poorly understood, especially since the polytrauma patients present a highly variable patient cohort with complex injury patterns, comorbidities and different therapeutic strategies.

Therefore, the present "NTF_PT_2014" multicenter study of the Trauma Research Network (NTF) of the German Society for Orthopaedics and Trauma (DGOU) with its established national Polytrauma-serum-bank aims to collect, store, and analyse plasma and serum from polytrauma-patients and corresponding clinical data to address:

1. how trauma modulates the release of danger molecules, inflammatory mediators, coagulation factors and novel biomarkers?
2. how the specific injury pattern affects the posttraumatic response and regenerative potential on a organ-, cell, and molecular level?
3. how could a specific organ- and immune-monitoring predict the clinical outcome?

Blood will be drawn from anticipated 1000 patients with an injury severity score ≥ 25 at the time of hospital admission (in the emergency room), 8 h, 24h, 48, 120 h, and 240 h post injury. The biochemical and immune-monitoring data will be correlated to corresponding clinical data and data from the German Trauma Registry (TraumaRegister DGU®).

Blood from age- and sex matched healthy volunteers (n=200) will serve as a control group.

The study will provide a detailed picture of the molecular danger response after multiple injury and may reveal novel therapeutic targets for posttraumatic complications.

• Study Type: Observational
• Enrollment (Anticipated): 1000

Contacts and Locations

Study Locations

• Germany
  • Baden-Wuerttemberg
    • Ulm, Baden-Wuerttemberg, Germany, 89081
      • Recruiting
      • University Hospital
      • Contact: Markus S Huber-Lang, M.D., Prof.; Phone Number: 54717 0049-731-5000; Email: markus.huber-lang@uniklinik-ulm.de
      • Contact: Manfred Weiss, M.D., Prof.; Phone Number: 60226 0049-731-5000; Email: manfred.weiss@uniklinik-ulm.de
      • Principal Investigator: Mario Perl, M.D., Prof.
      • Sub-Investigator: Ingo Marzi, M.D., Prof.
      • Sub-Investigator: Martijn Van Griensven, M.D., Prof.
      • Sub-Investigator: Roman Pfeiffer, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

polytrauma patients age ≥ 18 ISS ≥ 25

Exclusion: cardiopulmonary reanimation before admission, gravidity, no chemotherapy or radiotherapy within the last 3 months, immune supressive drugs, hemodialysis, age < 18

Description

Inclusion Criteria:

• age ≥ 18
• healthy

Exclusion Criteria:

• age < 18
• gravidity

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Ctrl; healthy volunteers, sex- and age matched Blood drawing at one time point: 20 ml	Procedure: blood drawing; blood drawing
PT; polytrauma patients fulfilling the following criteria: injury severity score ≥25; age ≥ 18 Blood drawing at admission to the emergency room, 8 h, 24h, 48 h, 120 h and 240 h post trauma: 20 ml	Procedure: blood drawing; blood drawing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Interleukin-6 (IL-6) plasma concentration	Interleukin-6 may indicate the extent of tissue damage and the inflammatory response after trauma	24 hours after polytrauma

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Multiple-Organ-Failure (MOF)	daily "Sequential Organ Failure Assessment" score	0-28 days after trauma
Sepsis	sepsis definition daily in accordance to the "American College of Chest Physicians/Society of Critical Care Medicine" Consensus	0-28 days after trauma
S100 calcium-binding protein B plasma concentration	plasma S100 calcium-binding protein B as a marker for central nervous system injury	within 30 minutes after polytrauma/ 8 hours/ 24 hours/ 48 hours/ 120 hours/240 hours after polytrauma
Creatinine plasma concentration	plasma creatinine to measure the glomerular filtration rate as a marker of renal function.	within 30 minutes after polytrauma/ 8 hours/ 24 hours/ 48 hours/ 120 hours/240 hours after polytrauma
Bilirubin plasma concentration	plasma bilirubin as a biomarker for liver failure	within 30 minutes after polytrauma/ 8 hours/ 24 hours/ 48 hours/ 120 hours/240 hours after polytrauma
Survival	survival recorded every day: yes/no	28-day survival
monomeric C-reactive protein	C-reactive protein may not only represent a biomarker of the systemic inflammatory response after trauma but also help to clear danger- and pathogen-associated molecular patterns	within 30 minutes after polytrauma/ 8 hours/ 24 hours/ 48 hours/ 120 hours/240 hours after polytrauma
pentameric C-reactive protein	C-reactive protein may not only represent a biomarker of the systemic inflammatory response after trauma but also help to clear danger- and pathogen-associated molecular patterns	within 30 minutes after polytrauma/ 8 hours/ 24 hours/ 48 hours/ 120 hours/240 hours after polytrauma
Interleukin-10	Inflammatory profiling: plasma concentrations of Interleukin-10	within 30 minutes after polytrauma/ 8 hours/ 24 hours/ 48 hours/ 120 hours/240 hours after polytrauma
Interleukin-1beta	Inflammatory profiling: plasma concentrations of Interleukin-1beta	within 30 minutes after polytrauma/ 8 hours/ 24 hours/ 48 hours/ 120 hours/240 hours after polytrauma
Complement factor C3a	Inflammatory profiling: plasma concentrations of Complement factor C3a	within 30 minutes after polytrauma/ 8 hours/ 24 hours/ 48 hours/ 120 hours/240 hours after polytrauma
Arterial partial oxygen pressure	Arterial partial oxygen pressure reflects lung performance	daily, the first 10 days after trauma
Number of microvesicles derived from granulocytes in plasma of patients (as assessed by flow cytometry)	Microvesicles as carriers of clotting factors and inflammatory molecules may be significantly involved in the coagulatory and inflammatory response after trauma	within 30 minutes after polytrauma/ 8 hours/ 24 hours/ 48 hours/ 120 hours/240 hours after polytrauma

Collaborators and Investigators

• Sponsor: University of Ulm
• Investigators: Study Director: Markus Huber-Lang, M.D. Prof, University of Ulm, Center for Biomedical Research (ZBF)

Publications and helpful links

General Publications

• Halbgebauer R, Karasu E, Braun CK, Palmer A, Braumuller S, Schultze A, Schafer F, Buckle S, Eigner A, Wachter U, Radermacher P, Resuello RRG, Tuplano JV, Nilsson Ekdahl K, Nilsson B, Armacki M, Kleger A, Seufferlein T, Kalbitz M, Gebhard F, Lambris JD, van Griensven M, Huber-Lang M. Thirty-Eight-Negative Kinase 1 Is a Mediator of Acute Kidney Injury in Experimental and Clinical Traumatic Hemorrhagic Shock. Front Immunol. 2020 Aug 26;11:2081. doi: 10.3389/fimmu.2020.02081. eCollection 2020.

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Anticipated): September 1, 2018
• Study Completion (Anticipated): October 1, 2018

Study Registration Dates

• First Submitted: January 19, 2016
• First Submitted That Met QC Criteria: February 10, 2016
• First Posted (Estimate): February 15, 2016

Study Record Updates

• Last Update Posted (Estimate): February 15, 2016
• Last Update Submitted That Met QC Criteria: February 10, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: sepsis; polytrauma; hemorrhagic shock; MODS
• Additional Relevant MeSH Terms: Wounds and Injuries; Multiple Trauma
• Other Study ID Numbers: NTF_PT_2014

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO