Effect of C1-esterase Inhibitor on Systemic Inflammation in Trauma Patients With a Femur or Pelvic Fracture
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- UMC Utrecht
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Delta Interleukine-6
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Multi trauma patients
- •Femur or pelvic fracture
- •Injury Severity Score (ISS) ≥ 18
- •Age 18-80 yrs
排除标准
- •Congenital C1-inhibitor deficiency
- •Use of immune suppressants
- •Pregnancy
- •Known hypersensitivity for blood products
- •Fixation of femur fracture with external fixation or osteosynthesis
研究组 & 干预措施
C1-esterase inhibitor
C1-esterase inhibitor, 100 U/kg bodyweight
干预措施: C1-esterase inhibitor (Drug)
Saline 0.9%
Saline 0.9%
干预措施: Saline 0.9% (Other)
结局指标
主要结局
Delta Interleukine-6
时间窗: 6 hours after C1-INH administration
次要结局
- Hemodynamic response(Up to 12 days after C1-INH administration)
- 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)
研究者
Prof. dr Leenen
L.P.H. Leenen, MD, PhD, UMC Utrecht.
UMC Utrecht