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

Sponsor

UMC Utrecht (Other)

Overall Status

Terminated

CT.gov ID

NCT01275976

Collaborator

Prothya Biosolutions (Industry)

Enrollment

Location

Arms

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

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

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

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

11 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

Triple (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

Study Start Date :

Apr 1, 2012

Actual Primary Completion Date :

Feb 1, 2015

Actual Study Completion Date :

Feb 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
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 Names: 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

Arm

Intervention/Treatment

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 Names:

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

Outcome Measures

Primary Outcome Measures

Delta Interleukine-6 [6 hours after C1-INH administration]

Secondary Outcome Measures

Cytokines and other markers of inflammation [up to 12 days after C1-INH administration]
Neutrophil redistribution and phenotype [Up to 12 days after C1-INH administration]
C1-inhibitor and complement concentration and activity [Up to 12 days after C1-INH administration]
Hemodynamic response [Up to 12 days after C1-INH administration]