Effect of Intrapulmonary Administration of Recombinant Human Activated Protein C on Local Coagulation and Inflammation After Bronchial Instillation of Lipopolysaccharide in Humans
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- To determine whether direct intrapulmonary delivery of rhAPC can inhibit LPS-induced lung inflammation, thereby avoiding systemic APC effects
研究概览
简要总结
Recombinant human Activated Protein C (rhAPC) has been shown to reduce the mortality of patients with severe sepsis. The biological effects of APC are pleiotropic, and can be roughly divided in anticoagulant and cytoprotective effects. Lung infection and inflammation are associated with reduced bronchoalveolar levels of endogenous APC. Recent evidence derived from animal studies indicates that local administration of rAPC into the lungs exerts local anti-inflammatory and anticoagulant effects. In this study we propose to study the potential of locally administered APC, within a lung subsegment, to inhibit lipopolysaccharide (LPS) induced lung inflammation and coagulation in humans.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Male, 18-35 years of age
- •No clinically significant findings during physical examination and hematological and biochemical screening
- •Normal spirometry and ECG
- •Able to communicate well with the investigator and to comply with the requirements of the study
- •No medication
- •Written informed consent
- •No smoking
- •Exclusion criteria:
- •Known diseases
- •A history of smoking within the last six months, or regular consumption of greater than three units of alcohol per day
- •Administration of any investigational drug within 30 days of study initiation
- •Donation of blood within 60 days, or loss of greater than 400 ml of blood within 12 weeks of study initiation
- •History of enhanced bleeding tendency
- •History of heparin-induced thrombocytopenia
- •History of serious drug-related reactions, including hypersensitivity
排除标准
- 未提供
研究组 & 干预措施
Activated protein C
干预措施: Drotrecogin alpha (Drug)
Activated protein C
干预措施: Endotoxin (Drug)
Activated protein C
干预措施: Bronchoscopy (Procedure)
Activated protein C
干预措施: Blood sampling (Procedure)
Saline
干预措施: Saline (NaCl 0.9%) (Drug)
Saline
干预措施: Endotoxin (Drug)
Saline
干预措施: Bronchoscopy (Procedure)
Saline
干预措施: Blood sampling (Procedure)
结局指标
主要结局
To determine whether direct intrapulmonary delivery of rhAPC can inhibit LPS-induced lung inflammation, thereby avoiding systemic APC effects
时间窗: 1 year
次要结局
- 1. Neutrophil responses 2. Response of alveolar macrophages 3. Activation of the cytokine and chemokine network 4. Activation of coagulation and fibrinolysis(1 year)