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

This study is currently recruiting participants.
Verified April 2013 by UMC Utrecht
Sponsor:
Collaborator:
Sanquin
Information provided by (Responsible Party):
Prof. dr Leenen, UMC Utrecht
ClinicalTrials.gov Identifier:
NCT01275976
First received: January 12, 2011
Last updated: April 4, 2013
Last verified: April 2013
History of Changes
  Purpose

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


Condition Intervention Phase
Trauma
Inflammation
Sepsis
Multiple Organ Dysfunction Syndrome
 Drug: C1-esterase inhibitor
Other: Saline 0.9%
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Effect of C1-esterase Inhibitor on Systemic Inflammation in Trauma Patients With a Femur or Pelvic Fracture

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by UMC Utrecht:

Primary Outcome Measures:
  • Delta Interleukine-6 [ Time Frame: 6 hours after C1-INH administration ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Cytokines and other markers of inflammation [ Time Frame: up to 12 days after C1-INH administration ] [ Designated as safety issue: No ]
  • Neutrophil redistribution and phenotype [ Time Frame: Up to 12 days after C1-INH administration ] [ Designated as safety issue: No ]
  • C1-inhibitor and complement concentration and activity [ Time Frame: Up to 12 days after C1-INH administration ] [ Designated as safety issue: No ]
  • Hemodynamic response [ Time Frame: Up to 12 days after C1-INH administration ] [ Designated as safety issue: No ]

Estimated Enrollment: 70
Study Start Date: April 2012
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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%
Saline 0.9%
 Other: Saline 0.9%
Infusion, just before the start of the femur or pelvic fixation operation

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

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01275976

Contacts
Contact: Luke P Leenen, MD, PhD +31887559982 l.p.h.leenen@umcutrecht.nl
Contact: Marjolein Heeres, MD +31887558552 m.heeres-2@umcutrecht.nl

Locations
Netherlands
University Medical Centre Utrecht Recruiting
Utrecht, Netherlands, 3508 GA
Contact: Luke P Leenen, Md, PhD     +31887559982     l.p.h.leenen@umcutrecht.nl    
Sponsors and Collaborators
UMC Utrecht
Sanquin
Investigators
Principal Investigator: Luke P Leenen, MD, PhD UMC Utrecht
  More Information

No publications provided by UMC Utrecht

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Prof. dr Leenen, L.P.H. Leenen, MD, PhD, UMC Utrecht., UMC Utrecht
ClinicalTrials.gov Identifier: NCT01275976     History of Changes
Other Study ID Numbers: 34932
Study First Received: January 12, 2011
Last Updated: April 4, 2013
Health Authority: Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by UMC Utrecht:
C1-esterase inhibitor
Systemic inflammation
Sepsis
 Trauma
Multiple Organ Dysfunction Syndrome
Cytokines

Additional relevant MeSH terms:
Inflammation
Multiple Organ Failure
Sepsis
Wounds and Injuries
Pathologic Processes
Shock
Infection
Systemic Inflammatory Response Syndrome
Complement C1 Inactivator Proteins
 Complement C1 Inhibitor Protein
Complement C1
Complement C1s
Complement Inactivating Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 19, 2013