Danger Response in Polytrauma Patients

Study Overview
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Brief Summary
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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.

Detailed Description
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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: how trauma modulates the release of danger molecules, inflammatory mediators, coagulation factors and novel biomarkers? how the specific injury pattern affects the posttraumatic response and regenerative potential on a organ-, cell, and molecular level? 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.

Official Title
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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)

Conditions
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Multiple Trauma

Intervention / Treatment
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* Procedure: blood drawing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age ≥ 18 healthy Exclusion Criteria: age < 18 gravidity

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Ctrl<br>healthy volunteers, sex- and age matched Blood drawing at one time point: 20 ml | Procedure: blood drawing<br>* blood drawing<br>|
| PT<br>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<br>* blood drawing<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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polytrauma, hemorrhagic shock, sepsis, MODS