An Open-label Randomized Controlled Experimental Endotoxemia Study on the Effects of the Cytokine-adsorber CytoSorb on the Development of Immunoparalysis in Humans
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Between group differences in plasma interleukin (IL)-6 levels during the second endotoxin challenge.
研究概览
简要总结
In this randomized, open-label study, the investigators will assess whether CytoSorb hemoperfusion will prevent or attenuate the development of immunoparalysis in healthy volunteers undergoing repeated experimental endotoxemia.
详细描述
Sepsis is an inflammatory syndrome with high mortality rates and increasing incidence. Sepsis-induced immunoparalysis, increasingly recognized as the overriding immune disorder in sepsis patients, attributes significantly to late mortality in sepsis patients.
The investigators hypothesize that 'blood purification' techniques targeted at the removal of excess circulating cytokines, such as the CytoSorb hemoperfusion device, might prevent or attenuate the development of immunoparalysis.
The objective of this trial is to determine the effects of CytoSorb hemoperfusion on the development of immunoparalysis in a repeated experimental endotoxemia model in healthy male volunteers.
To this end, 24 healthy male volunteers subjects will be randomized in a 1:1 fashion into one of two treatment groups (active or control). Both study groups will undergo two endotoxin challenges, separated by seven days. To this end, endotoxin (LPS) will be administered as a bolus of 1 ng/kg, followed by continuous infusion of 0.5 ng/kg/hr for three hours. The active group will be treated with CytoSorb hemoperfusion during the first endotoxin challenge, whereas the control group will receive no additional treatment. During both endotoxin challenges, blood samples will be obtained serially to measure levels of circulating cytokines and other inflammatory mediators.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
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
- •Provide written informed consent
- •Age ≥ 18 and ≤ 35 years
- •Healthy (as determined by medical history, physical examination, vital signs, 12-lead electrocardiogram (ECG) and routine clinical laboratory parameters)
排除标准
- •Use of any medication
- •Known anaphylaxis or hypersensitivity to any (non-)investigational products or their excipients.
- •History or signs of atopic syndrome (asthma, rhinitis with medication and/or eczema)
- •History or signs of hematological disease
- •History or signs of thromboembolic disorders
- •History of (intracranial) aneurysmal or hemorrhagic diseases
- •History of heparin-induced thrombocytopenia (HIT)
- •Thrombocytopenia (<150*109/ml) or anemia (hemoglobin < 8.0 mmol/L)
- •History, signs or symptoms of cardiovascular disease, in particular:
- •Previous spontaneous vagal collapse
- •History of atrial or ventricular arrhythmia
- •Cardiac conduction abnormalities on the ECG consisting of a 2nd degree atrio-ventricular block or a complete left bundle branch block
- •Hypertension (defined as RR systolic > 160 or RR diastolic > 90 mmHg)
- •Hypotension (defined as RR systolic < 100 or RR diastolic < 50 mmHg)
- •Renal impairment (defined as plasma creatinine >120 μmol/l)
- •Liver enzyme abnormalities (above 2x the upper limit of normal)
- •Medical history of any disease associated with immune deficiency
- •Signs of infection (CRP > 20 mg/L, WBC > 12x109/L or < 4x109/L)
- •Clinically significant acute illness, including infections or trauma, within 1 month of the first endotoxin challenge
- •Previous (participation in a study with) endotoxin (LPS) administration
- •Any vaccination within 3 months within of the first endotoxin challenge
- •Participation in a drug trial or donation of blood within 3 months prior to first endotoxin challenge
- •Recent hospital admission or surgery with general anesthesia within 3 months prior to first endotoxin challenge
- •Use of recreational drugs within 1 month of the first endotoxin challenge
- •Inability to personally provide written informed consent (e.g. for linguistic or mental reasons) and/or take part in the study.
结局指标
主要结局
Between group differences in plasma interleukin (IL)-6 levels during the second endotoxin challenge.
时间窗: Samples will be obtained starting 1 hour prior until 8 hours after endotoxin administration
Blood samples will be obtained at predefined time points before, during and after endotoxin administration to assess plasma levels (in pg/mL) of circulating inflammatory mediatiors. To assess between group differences, the area under the curve (AUC) of the time concentration curve (expressed in arbitrary units) of each inflammatory mediator will be calculated.
次要结局
- Between group differences in norepinephrine sensitivity(One hour before and 4 hours after endotoxin administration during the first endotoxin challenge)
- Cytokine clearance by the adsorber(Every 30 minutes until cessation of hemoperfusion (six hours after endotoxin administration))
- Between group differences in body temperature(Every 30 minutes from 1 hour prior until 8 hours after endotoxin administration)
- Between group differences in blood pressure(From 1 hour prior until 8 hours after endotoxin administration)
- Between group differences in heart rate(From 1 hour prior until 8 hours after endotoxin administration)
- Between group differences in plasma levels of other inflammatory cytokines during the second endotoxin challenge.(Samples will be obtained starting 1 hour prior until 8 hours after endotoxin administration)
- Between group differences in endotoxemia-induced clinical symptoms(Every 30 minutes from 1 hour prior until 8 hours after endotoxin administration)
- Between group differences in markers of endothelial injury(Samples will be obtained starting 1 hour prior until 8 hours after endotoxin administration)
- Between group differences in mHLA-DR expression(1 hour before, 3 hours after and 6 hours after endotoxin administration)
- Between group differences in endotoxemia-induced metabolic activity of platelets(1 hour prior until 8 hours after endotoxin administration)