Effect of C1-esterase Inhibitor on Systemic Inflammation in Trauma Patients With a Femur or Pelvic Fracture (CAESAR)
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
|Trauma Inflammation Sepsis Multiple Organ Dysfunction Syndrome||Drug: C1-esterase inhibitor Other: Saline 0.9%||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double Blind (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
|Official Title:||Effect of C1-esterase Inhibitor on Systemic Inflammation in Trauma Patients With a Femur or Pelvic Fracture|
- Delta Interleukine-6 [ Time Frame: 6 hours after C1-INH administration ]
- Cytokines and other markers of inflammation [ Time Frame: up to 12 days after C1-INH administration ]
- Neutrophil redistribution and phenotype [ Time Frame: Up to 12 days after C1-INH administration ]
- C1-inhibitor and complement concentration and activity [ Time Frame: Up to 12 days after C1-INH administration ]
- Hemodynamic response [ Time Frame: Up to 12 days after C1-INH administration ]
|Study Start Date:||April 2012|
|Study Completion Date:||February 2015|
|Primary Completion Date:||February 2015 (Final data collection date for primary outcome measure)|
Active Comparator: C1-esterase inhibitor
C1-esterase inhibitor, 100 U/kg bodyweight
Drug: C1-esterase inhibitor
C1-esterase inhibitor 200 U/kg infusion over 30 minutes, just before the start of the femur or pelvic fixation operation.
Other Name: Cetor® (RVG 19303)
Placebo Comparator: Saline 0.9%
Other: Saline 0.9%
Infusion, just before the start of the femur or pelvic fixation operation
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01275976
|University Medical Centre Utrecht|
|Utrecht, Netherlands, 3508 GA|
|Principal Investigator:||Luke P Leenen, MD, PhD||UMC Utrecht|