Effect of C1-esterase Inhibitor on Systemic Inflammation in Trauma Patients With a Femur or Pelvic Fracture

Study Overview
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Brief Summary
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Trauma and major operation are associated with an excessive inflammation reaction due to tissue injury. This overwhelming immune response is considered to be a major risk factor in the pathogenesis of late inflammatory complications such as acute respiratory distress syndrome (ARDS), multiple organ dysfunction syndrome (MODS) and sepsis. The investigators hypothesize that administration of C1-esterase inhibitor (C1-INH) will attenuate the humane inflammatory response and, thereby, reduce the risk of inflammatory complications due to surgical interventions in trauma patients with a femur or pelvic fracture

Detailed Description
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Systemic inflammation in response to a femur or pelvic fracture and fixation is associated with complications, such as acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODS). The injury itself, but also the additional fixation procedure give a release of pro-inflammatory cytokines, in particular interleukin (IL)-6. This results in an aggravation of the initial systemic inflammatory response, and will cause in some patients an increased risk on the development of inflammatory complications, like ARDS and MODS. Which can lead to higher morbidity, mortality and prolonged hospital stay. Various strategies, such as damage control orthopedics, have been proposed to prevent these complications. Another strategy is to decrease the inflammatory reaction caused by the surgical procedure, and by interventions focused on inhibition of the innate inflammatory response. This will lower the risk of complications. A promising candidate is the endogenously produced serum protein C1-esterase inhibitor (C1-INH). This protein is an acute phase protein, produced by the liver in response to inflammatory conditions. C1-INH is a major inactivator of the complement system, but important additional anti-inflammatory properties have been demonstrated. A previous study of from our laboratory showed that administration of the drug C1-INH significantly reduced the concentration of circulating pro-inflammatory cytokines such as IL-6, during human experimental endotoxemia. Treatment with C1-INH has been proven to be safe in treatment with humans, even in high dosages and in pregnant patients with C1-INH deficiency.

Official Title
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Effect of C1-esterase Inhibitor on Systemic Inflammation in Trauma Patients With a Femur or Pelvic Fracture

Conditions
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Trauma, Inflammation, Sepsis, Multiple Organ Dysfunction Syndrome

Intervention / Treatment
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* Drug: C1-esterase inhibitor
* Other: Saline 0.9%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Multi trauma patients Femur or pelvic fracture Injury Severity Score (ISS) ≥ 18 Age 18-80 yrs Exclusion Criteria: Congenital C1-inhibitor deficiency Use of immune suppressants Pregnancy Known hypersensitivity for blood products Fixation of femur fracture with external fixation or osteosynthesis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: C1-esterase inhibitor<br>C1-esterase inhibitor, 100 U/kg bodyweight | Drug: C1-esterase inhibitor<br>* C1-esterase inhibitor 200 U/kg infusion over 30 minutes, just before the start of the femur or pelvic fixation operation.<br>* Other names: Cetor® (RVG 19303);|
| Placebo Comparator: Saline 0.9%<br>Saline 0.9% | Other: Saline 0.9%<br>* Infusion, just before the start of the femur or pelvic fixation operation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delta Interleukine-6 |  | 6 hours after C1-INH administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cytokines and other markers of inflammation |  | up to 12 days after C1-INH administration | 
| Neutrophil redistribution and phenotype |  | Up to 12 days after C1-INH administration | 
| C1-inhibitor and complement concentration and activity |  | Up to 12 days after C1-INH administration | 
| Hemodynamic response |  | Up to 12 days after C1-INH administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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C1-esterase inhibitor, Systemic inflammation, Sepsis, Trauma, Multiple Organ Dysfunction Syndrome, Cytokines