Pediatric Immune Response to Infectious Shock (PedIRIS)
Infectious shocks are associated with high mortality rates (20-40%). Anti-inflammatory strategies based on the postulate that mortality related to sepsis is mainly due to an overwhelming pro-inflammatory immune response have failed. Some patients surviving this initial phase can develop immune dysfunctions because the compensatory mechanisms become deleterious when they persist over time. The persistence of immunosuppression at day 3 or 5 is independently associated with more nosocomial infections and higher mortality rate. The clinical and laboratory evidence for sepsis induced immunosuppression have been recently reviewed by Hotchkiss et al. Apoptosis-induced depletion of immune effector and blood studies from septic patients showed decreased production of pro-inflammatory cytokines, decreased HLA-DR expression, increased percentage of regulatory T cells, and increased production of programmed cell death (PD)-1. Some small positive phase 2 trials of biomarker guided immune enhancing agents granulocyte-macrophage colony stimulating factor (GM-CSF) and interferon γ (IFN γ) have been reported.
There are insufficient data showing that such an immunosuppression exists in children. Only one study performed in children with organ dysfunctions admitted to pediatric intensive care unit (PICU), showed that 34% of them developed immunosuppression. This study was performed on a heterogeneous population and immunological analyses were limited. Therefore, there is a crucial need of studies on septic patients with matched controls to provide more evidence that the same paradigm exists in children. The collaboration of laboratories with a high level of experience in this domain, and a clinical unit with a high potential of recruitment of children with severe infectious shock should allow us to perform the first prospective study specifically done in children with infectious shock.
The main hypothesis is that children with severe infectious shock developed sepsis-induced immunosuppression as shown in adults. This will be assessed by the expression of HLA-DR on monocytes' surface. We make the hypothesis that children who become immunosuppressed are more prone to develop secondary nosocomial infectious and stayed longer in PICU and in hospital.
Children aged from 1 month to 17 years, admitted to PICU at HFME Lyon-Bron are eligible if they have the criteria for severe sepsis or septic shock, defined by the "Surviving Sepsis Campaign 2012" or those of Toxic Shock Syndrome (TSS) (definitions of CDC - Center for Disease Control). An information leaflet will be issued to parents and children / adolescents and they will be informed of their right to object to the search. Are provided as part of this research:
- Immunological measures (mHLA -DR) in three stages: in the first 48 hours, between D3/5 and D7/9. The volume of collected blood will not exceed 2.4 ml / kg.
- The collection of nosocomial infections and status at D30 A control group of patients hospitalized for surgery without sepsis or toxic shock criteria will be recruited in the same hospital by ICU investigators and matched for age. Similarly controls will be given oral and written information and they will have the opportunity to deny inclusion. They will have the same exams as the first group of patients.
研究概览
研究类型
注册 (实际的)
阶段
- 不适用
联系人和位置
学习地点
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Lyon、法国
- Hospices Civils De Lyon
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria Infectious shock group:
- Children aged from 1 month to <18 years
- Diagnosis of severe infectious shock at PICU or within the first 24 hours following PICU admission: severe sepsis or septic shock, defined by Surviving Sepsis Campaign 2012, or Toxic Shock Syndrome, defined by CDC criteria.
Inclusion Criteria Control group:
- Healthy children aged matched to cases
- Hospitalized for an elective surgery (dental, ENT, maxillofacial, urologic, hernia surgery, neurosurgery without massive hemorrhage)
- Without any criteria of infection.
Exclusion Criteria (both groups):
- Chronic inflammatory disease;
- Immunodeficiency;
- Long-term corticosteroids;
- Ongoing immunosuppressive treatment;
- Transplanted patients;
- Tumors, hematological diseases;
- No health insurance coverage;
- Refusal to participate (from parents and/or patient) or inability to understand information.
学习计划
研究是如何设计的?
设计细节
- 主要用途:基础科学
- 分配:非随机化
- 介入模型:并行分配
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
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其他:Children with infectious shock
Children aged from 1 month to <18 years.
In 3 stratified groups : <2 years, 2-8 years, and >8 years.
About one third of the patients are expected in each age-group.
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其他:Control group: healthy children
Healthy children aged-matched to cases (same stratification group, about 20 per age group); They will be hospitalized for an elective surgery (dental, ENT, maxillofacial, urologic, hernia surgery, neurosurgery without massive hemorrhage) and without any infection.
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
---|---|---|
proportion of patients with a mHLA-DR level <30%
大体时间:up to Day 9
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mHLA-DR is measured by flow cytometry
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up to Day 9
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proportion of patients with a mHLA-DR level significantly lower than healthy children.
大体时间:in the pre-operative period
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mHLA-DR is measured by flow cytometry
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in the pre-operative period
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
total lymphocytes
大体时间:Day 1
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From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies
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Day 1
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total lymphocytes
大体时间:between Day 3 and day 5
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From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies
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between Day 3 and day 5
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total lymphocytes
大体时间:between Day 7 and day 9
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From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies
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between Day 7 and day 9
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levels of CD4+
大体时间:Day 1
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From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies
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Day 1
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levels of CD4+
大体时间:between Day 3 and day 5
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From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies
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between Day 3 and day 5
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levels of CD4+
大体时间:between Day 7 and day 9
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From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies
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between Day 7 and day 9
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levels of CD25+
大体时间:day 1
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From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies
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day 1
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levels of CD25+
大体时间:between Day 3 and day 5
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From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies
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between Day 3 and day 5
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levels of CD25+
大体时间:between Day 7 and day 9
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From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies
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between Day 7 and day 9
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levels of T lymphocytes (Treg)
大体时间:Day 1
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From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies
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Day 1
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levels of T lymphocytes (Treg)
大体时间:between Day 3 and day 5
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From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies
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between Day 3 and day 5
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levels of T lymphocytes (Treg)
大体时间:between Day 7 and day 9
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From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies
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between Day 7 and day 9
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dosage of cytokines
大体时间:Day 1
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Day 1
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dosage of cytokines
大体时间:between Day 3 and day 5
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between Day 3 and day 5
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dosage of cytokines
大体时间:between Day 7 and day 9
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between Day 7 and day 9
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Number of nosocomial infections
大体时间:up to Day 30
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up to Day 30
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Type of nosocomial infections
大体时间:up to Day 30
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bacteremia, ventilator-associated pneumonia, urinary tract infection, other sites.
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up to Day 30
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Mortality
大体时间:up to Day 30
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up to Day 30
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Length of vasoactive treatments
大体时间:up to Day 30
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up to Day 30
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合作者和调查者
调查人员
- 首席研究员:Etienne JAVOUHEY、Hospices Civils De Lyon
出版物和有用的链接
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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