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

UMC Utrecht

Status and phase: Terminated; Phase 3

Conditions: Inflammation; Multiple Organ Dysfunction Syndrome; Trauma; Sepsis

Treatments: Drug: C1-esterase inhibitor; Other: Saline 0.9%

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01275976

34932

Details and patient eligibility

About

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

Full 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.

Enrollment: 11 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Triple Blind

---

11 participants in 2 patient groups, including a placebo group

C1-esterase inhibitor

Active Comparator group

Description:

C1-esterase inhibitor, 100 U/kg bodyweight

Treatment:

Drug: C1-esterase inhibitor

Saline 0.9%

Placebo Comparator group

Description:

Saline 0.9%

Treatment:

Other: Saline 0.9%