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

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ClinicalTrials.gov Identifier: NCT01275976
Recruitment Status : Terminated (Futility and limited feasibility)
First Posted : January 13, 2011
Last Update Posted : February 4, 2015
Sponsor:
Collaborator:
Sanquin
Information provided by (Responsible Party):
Prof. dr Leenen, UMC Utrecht

January 12, 2011
January 13, 2011
February 4, 2015
April 2012
February 2015   (Final data collection date for primary outcome measure)
Delta Interleukine-6 [ Time Frame: 6 hours after C1-INH administration ]
Same as current
Complete list of historical versions of study NCT01275976 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Cytokines and other markers of inflammation [ Time Frame: up to 7 days after C1-INH administration ]
  • Neutrophil redistribution and phenotype [ Time Frame: Up to 7 days after C1-INH administration ]
  • C1-inhibitor and complement concentration and activity [ Time Frame: Up to 7 days after C1-INH administration ]
  • Hemodynamic response [ Time Frame: Up to 7 days after C1-INH administration ]
Not Provided
Not Provided
 
Effect of C1-esterase Inhibitor on Systemic Inflammation in Trauma Patients With a Femur or Pelvic Fracture
Effect of C1-esterase Inhibitor on Systemic Inflammation in Trauma Patients With a Femur or Pelvic Fracture

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

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.

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
  • Trauma
  • Inflammation
  • Sepsis
  • Multiple Organ Dysfunction Syndrome
  • 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)
  • Other: Saline 0.9%
    Infusion, just before the start of the femur or pelvic fixation operation
  • Active Comparator: C1-esterase inhibitor
    C1-esterase inhibitor, 100 U/kg bodyweight
    Intervention: Drug: C1-esterase inhibitor
  • Placebo Comparator: Saline 0.9%
    Saline 0.9%
    Intervention: Other: Saline 0.9%
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
11
70
February 2015
February 2015   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years to 80 Years   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
Netherlands
 
 
NCT01275976
34932
Yes
Not Provided
Not Provided
Prof. dr Leenen, UMC Utrecht
UMC Utrecht
Sanquin
Principal Investigator: Luke P Leenen, MD, PhD UMC Utrecht
UMC Utrecht
February 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP