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

Condition(s) targeted: Trauma; Inflammation; Sepsis; Multiple Organ Dysfunction Syndrome

Intervention: C1-esterase inhibitor (Drug); Saline 0.9% (Other)

Phase: Phase 3

Status: Recruiting

Sponsored by: UMC Utrecht

Official(s) and/or principal investigator(s):
Luke P Leenen, MD, PhD, Principal Investigator, Affiliation: UMC Utrecht

Overall contact:
Luke P Leenen, MD, PhD, Phone: +31887559982, Email: l.p.h.leenen@umcutrecht.nl

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 fracture

Official title: Effect of C1-esterase Inhibitor on Systemic Inflammation in Trauma Patients With a Femur Fracture

Study design: Allocation: Randomized, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Primary outcome: Delta Interleukine-6

Secondary outcome:

Cytokines and other markers of inflammation

Neutrophil redistribution and phenotype

C1-inhibitor and complement concentration and activity

Hemodynamic response

Detailed description: Systemic inflammation in response to femur 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.

Minimum age: 18 Years. Maximum age: 80 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Multi trauma patients

- Femur 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

Luke P Leenen, MD, PhD, Phone: +31887559982, Email: l.p.h.leenen@umcutrecht.nl

University Medical Centre Utrecht, Utrecht 3508 GA, Netherlands; Recruiting
Luke P Leenen, Md, PhD, Phone: +31887559982, Email: l.p.h.leenen@umcutrecht.nl

Starting date: April 2012
Last updated: May 9, 2012