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

NCT ID: NCT01275976

Last Updated: 2015-02-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-04-30
• Study Completion Date: 2015-02-28

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

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.

Conditions

Trauma; Inflammation; Sepsis; Multiple Organ Dysfunction Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

C1-esterase inhibitor

C1-esterase inhibitor, 100 U/kg bodyweight

Group Type: ACTIVE_COMPARATOR

C1-esterase inhibitor

Intervention Type: DRUG

C1-esterase inhibitor 200 U/kg infusion over 30 minutes, just before the start of the femur or pelvic fixation operation.

Saline 0.9%

Saline 0.9%

Group Type: PLACEBO_COMPARATOR

Saline 0.9%

Intervention Type: OTHER

Infusion, just before the start of the femur or pelvic fixation operation

Interventions

C1-esterase inhibitor

C1-esterase inhibitor 200 U/kg infusion over 30 minutes, just before the start of the femur or pelvic fixation operation.

Intervention Type: DRUG

Saline 0.9%

Infusion, just before the start of the femur or pelvic fixation operation

Intervention Type: OTHER

Other Intervention Names

Cetor® (RVG 19303)

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Prothya Biosolutions

INDUSTRY

Sponsor Role: collaborator

UMC Utrecht

OTHER

Sponsor Role: lead

Responsible Party

Prof. dr Leenen

L.P.H. Leenen, MD, PhD, UMC Utrecht.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Luke P Leenen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

UMC Utrecht

Locations

University Medical Centre Utrecht

Utrecht, , Netherlands

Countries

Netherlands

References

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.

Reference Type: DERIVED

PMID: 21988742 (View on PubMed)

Other Identifiers

34932

Identifier Type: -

Identifier Source: org_study_id