Clinical trial NCT01275976: Effect of C1-esterase Inhibitor on Systemic Inflammation in Trauma Patients With a Femur or Pelvic Fracture
Official title: Effect of C1-esterase Inhibitor on Systemic Inflammation in Trauma Patients With a Femur or Pelvic Fracture
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Trauma
Inflammation
Sepsis
Multiple Organ Dysfunction Syndrome
Keywords: C1-esterase inhibitor
Systemic inflammation
Sepsis
Trauma
Multiple Organ Dysfunction Syndrome
Cytokines
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: Prothya Biosolutions
First posted: 2011-01-13
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Delta Interleukine-6
timeFrame: 6 hours after C1-INH administration
Secondary outcomes:
measure: Cytokines and other markers of inflammation
timeFrame: up to 12 days after C1-INH administration
measure: Neutrophil redistribution and phenotype
timeFrame: Up to 12 days after C1-INH administration
measure: C1-inhibitor and complement concentration and activity
timeFrame: Up to 12 days after C1-INH administration
measure: Hemodynamic response
timeFrame: Up to 12 days after C1-INH administration
Other outcomes:
Locations:
city: Utrecht
country: Netherlands
facility: University Medical Centre Utrecht
Study officials:
affiliation: UMC Utrecht
name: Luke P Leenen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Heeres M, Visser T, van Wessem KJ, Koenderman AH, Strengers PF, Koenderman L, Leenen LP. The effect of C1-esterase inhibitor on systemic inflammation in trauma patients with a femur fracture - The CAESAR study: study protocol for a randomized controlled trial. Trials. 2011 Oct 11;12:223. doi: 10.1186/1745-6215-12-223.