Prospective, Randomized Multicenter Trial of Adjunctive Intravenous Therapy With Sodium-selenite(Selenase®, Double-blinded) and a Procalcitonin Guided Causal Therapy (Open) of Severe Sepsis or Septic Shock.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,089
- 试验地点
- 35
- 主要终点
- All cause mortality
研究概览
简要总结
Severe sepsis and septic shock are diseases of infectious origin with a high risk of death. The purpose of this study is to determine whether the intravenous application of selenium (given as sodium-selenite) can reduce mortality in patients with severe sepsis or septic shock. Additionally, it is investigated, whether the measurement of procalcitonin - a marker of infection - can be used to guide anti-infectious measures in this disease.
详细描述
This is a multicenter trial of the German Network Sepsis (SepNet) on patients with severe sepsis or septic shock. This study is supported by unrestricted grants.
The release of reactive oxygen species is an important factor in the development of sepsis induced multiorgan dysfunction syndrome. Common protection mechanisms are impaired in this syndrome. Serum levels of selenium, a cofactor of the glutathionperoxidase, are reduced. Several studies suggest a benefit of selenium application in patients with severe sepsis but data from large clinical trials are not available. After inclusion into the study, patients are randomly allocated to a placebo or selenium group. Treating physicians and patients are blinded regarding the allocation. The selenium group receives sodium selenite intravenously - 1000 µg as a bolus followed by a continuous infusion of 1000 µg per day until the end of ICU treatment but not longer than 21 days.
Procalcitonin (PCT) is a biomarker which is elevated in the blood of patients with severe sepsis/septic shock. Data from patients with community acquired pneumonia demonstrated that this biomarker can be used to decide on the duration of antimicrobial therapy. Studies with small sample size seem to confirm this in ICU patients with severe sepsis. However, this needs to be confirmed in a larger cohort. All patients are randomly allocated to a PCT guided algorithm or a control group. In the PCT-guided group, PCT is measured at randomization, day 4, 7, 10, and 14. Depending on the PCT course, the protocol recommends to change, alter, or stop anti-infectious measures. In the control group, anti-infectious therapy is left to the discretion of the treating physician.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Severe sepsis or septic shock according to ACCP/SCCM criteria
- •Onset of severe sepsis or septic shock <24 h
- •Age >= 18 years
- •Informed consent
排除标准
- •Pregnant or breast-feeding women
- •Fertile female women without effective contraception
- •Participation in interventional clinical trial within the last 30 days
- •Current participation in any study
- •Former participation in this trial
- •Selenium intoxication
- •No commitment to full patient support (i.e. DNR order)
- •Patient's death is considered imminent due to coexisting disease
- •Relationship of the patient to study team member (i.e. colleague, relative)
- •Infection where guidelines recommend a longer duration of antimicrobial therapy (i.e. endocarditis, tuberculosis, malaria etc)
- •Immunocompromised patients
研究组 & 干预措施
SelPCT
Patient receives sodium-selenite; causal therapy is guided by a PCT based algorithm.
干预措施: sodium-selenite (Drug)
SelPCT
Patient receives sodium-selenite; causal therapy is guided by a PCT based algorithm.
干预措施: Procalcitonin guided therapy (Procedure)
SelKon
Patient receives sodium-selenite; causal therapy is not guided by a PCT based algorithm.
干预措施: sodium-selenite (Drug)
PlacPCT
Patient receives placebo; causal therapy is guided by a PCT based algorithm.
干预措施: Placebo (Drug)
PlacPCT
Patient receives placebo; causal therapy is guided by a PCT based algorithm.
干预措施: Procalcitonin guided therapy (Procedure)
PlacKon
Patient receives placebo; causal therapy is not guided by a PCT based algorithm.
干预措施: Placebo (Drug)
结局指标
主要结局
All cause mortality
时间窗: 28 days
次要结局
- Mean total SOFA and SOFA subscores(study duration)
- All cause mortality(90 days)
- Frequency and duration of mechanical ventilation(90 days)
- Frequency and duration of vasopressor support(90 days)
- Frequency of adverse events and severe adverse events(study duration)
- Duration of antimicrobial therapy(study duration)
- Clinical cure and microbiological cure(days 4, 7, 10, 14)
- Costs of antimicrobial therapy(study duration)
- Time to change of antibiotic therapy(duration of study)
- Days alive without antimicrobial therapy(study duration)
- Frequency of resistancies against antibiotics (VRE, MRSA, ESBL)(study duration)
- ICU length of stay(90 days)
- Hospital length of stay(90 days)
- Rate of surgical procedures for focus control(study duration)
- Rate of procedures to diagnose infections(study duration)
- Frequency of new infections(study duration)