Clinical trial NCT00710411: Inflammatory Response After Muscle and Skeleton Trauma
Official title: Inflammatory Response in Polytraumatized Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Multiple Trauma
Keywords: humans
patients
polytrauma
complement
inflammation
inflammatory response
biomarkers
cytokines
cell surface markers
apoptosis
NF-kappaB
functional polymorphisms
mesenchymal stem cell
severity of injury
ISS
infections
systemic inflammatory response syndrome
SIRS
sepsis
severe sepsis
shock
organ dysfunctions
SOFA
severity of disease
APACHEII
SAPSII
SPAPS3
length of stay
wound healing
outcome
mortality
Lead sponsor: University of Ulm
Sponsor class: OTHER
Collaborators: name: German Research Foundation
First posted: 2008-07-04
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Polytraumatized patients with an ISS \> 18 Controls: healthy volunteers

Brief summary: The purpose of this study is to determine the inflammatory response after multiple trauma in humans.

Detailed description: Polytraumatized patients are via a systemic inflammatory response syndrome at high risk for an uneventful outcome in the posttraumatic phase. One of the main functions of the inflammatory response is the recognition and elimination of damaged tissues and microorganisms. In polytraumatized patients, a huge amount of damaged cells occurs which has to be eliminated by programmed cell death (apoptosis)without damaging surrounding tissues. It remains unclear whether, when and how an interplay of complement system, NF-kB, danger and pattern recognition receptors, apoptosis, mesenchymal stem cells and their regulation may be beneficial and harmful. Differing activation of the complement system, pro-inflammatory biomarkers and predisposing polymorphisms of response and receptor genes are expected to lead to varying outcome. Therefore, this prospective observational study will enroll n=60 polytraumatized patients with an ISS\>18 to monitor longitudinally their inflammatory response after trauma and to find out whether there is a discriminating pattern of the cross talk between complement system, biomarkers and apoptosis in patients with beneficial or harmful outcome.

Eligibility criteria: Inclusion Criteria:

* multiple trauma injury, injury severity score (ISS) \> 18 with

  1. isolated fractures of the extremities
  2. fractures of the extremities combined with blunt/penetrating visceral trauma
  3. fractures of the extremities combined with blunt/penetrating thoracic trauma
  4. isolated head injury with morphological changes in CCT
  5. combination of points 1 - 4

     Exclusion Criteria:
* life expectancy \< 24 hours
* participation in other trials
* ISS \< 18
* cardiopulmonary reanimation on the accident scene or dying immediately after hospital admission
* age \< 18 years
* known or suspected pregnancy
* patients with ray-treatment or chemotherapy within the last three months

Primary outcomes:
measure: Inflammatory pattern of complement activation, biomarkers and complement-regulating proteins (CRegs)on leukocytes
timeFrame: 0, 1, 4, 12, 24, 48, 96, 120 und 240 h after trauma
Secondary outcomes:
measure: inflammatory biomarkers, cell surface markers, apoptosis, functional polymorphisms, mesenchymal stem cells, severity of injury (ISS), infections, SIRS, sepsis, shock, organ dysfunctions, severity of disease, ICU length of stay, wound healing, mortality
timeFrame: 0, 1, 4, 12, 24, 48, 96, 120 und 240 h after trauma for biochemical and immunological parameters; ISS on admission; scores on a daily basis; ICU and hospital death on discharge
Other outcomes:
Locations:
city: Ulm
country: Germany
facility: Clinic of Anesthesiology and Clinic of Traumatology, Hand-, Plastic-, and Reconstructive Surgery
Study officials:
affiliation: Clinic of Anesthesiology, University Hospital Medical School, Steinhoevelstrasse 9, 89070 Ulm, Germany
name: Manfred M Weiss, MD, MBA
role: PRINCIPAL_INVESTIGATOR
References:
citation: Huber-Lang M, Denk S, Fulda S, Erler E, Kalbitz M, Weckbach S, Schneider EM, Weiss M, Kanse SM, Perl M. Cathepsin D is released after severe tissue trauma in vivo and is capable of generating C5a in vitro. Mol Immunol. 2012 Feb;50(1-2):60-5. doi: 10.1016/j.molimm.2011.12.005. Epub 2012 Jan 14.
citation: Unnewehr H, Rittirsch D, Sarma JV, Zetoune F, Flierl MA, Perl M, Denk S, Weiss M, Schneider ME, Monk PN, Neff T, Mihlan M, Barth H, Gebhard F, Ward PA, Huber-Lang M. Changes and regulation of the C5a receptor on neutrophils during septic shock in humans. J Immunol. 2013 Apr 15;190(8):4215-25. doi: 10.4049/jimmunol.1200534. Epub 2013 Mar 11.
citation: Denk S, Wiegner R, Hones FM, Messerer DA, Radermacher P, Weiss M, Kalbitz M, Ehrnthaller C, Braumuller S, McCook O, Gebhard F, Weckbach S, Huber-Lang M. Early Detection of Junctional Adhesion Molecule-1 (JAM-1) in the Circulation after Experimental and Clinical Polytrauma. Mediators Inflamm. 2015;2015:463950. doi: 10.1155/2015/463950. Epub 2015 Oct 18.
citation: Kozarcanin H, Lood C, Munthe-Fog L, Sandholm K, Hamad OA, Bengtsson AA, Skjoedt MO, Huber-Lang M, Garred P, Ekdahl KN, Nilsson B. The lectin complement pathway serine proteases (MASPs) represent a possible crossroad between the coagulation and complement systems in thromboinflammation. J Thromb Haemost. 2016 Mar;14(3):531-45. doi: 10.1111/jth.13208. Epub 2016 Feb 15.