Severe Pediatric Infectious Shock Clinical Trial
— PedIRISOfficial title:
Pediatric Immune Response to Infectious Shock
| Verified date | November 2018 |
| Source | Hospices Civils de Lyon |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 105 |
| Est. completion date | August 4, 2018 |
| Est. primary completion date | August 4, 2018 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | All |
| Age group | 1 Month to 17 Years |
| Eligibility |
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. |
| Country | Name | City | State |
|---|---|---|---|
| France | Hospices Civils de Lyon | Lyon |
| Lead Sponsor | Collaborator |
|---|---|
| Hospices Civils de Lyon |
France,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | proportion of patients with a mHLA-DR level <30% | mHLA-DR is measured by flow cytometry | up to Day 9 | |
| Primary | proportion of patients with a mHLA-DR level significantly lower than healthy children. | mHLA-DR is measured by flow cytometry | in the pre-operative period | |
| Secondary | total lymphocytes | From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies | Day 1 | |
| Secondary | total lymphocytes | From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies | between Day 3 and day 5 | |
| Secondary | total lymphocytes | From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies | between Day 7 and day 9 | |
| Secondary | levels of CD4+ | From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies | Day 1 | |
| Secondary | levels of CD4+ | From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies | between Day 3 and day 5 | |
| Secondary | levels of CD4+ | From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies | between Day 7 and day 9 | |
| Secondary | levels of CD25+ | From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies | day 1 | |
| Secondary | levels of CD25+ | From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies | between Day 3 and day 5 | |
| Secondary | levels of CD25+ | From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies | between Day 7 and day 9 | |
| Secondary | levels of T lymphocytes (Treg) | From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies | Day 1 | |
| Secondary | levels of T lymphocytes (Treg) | From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies | between Day 3 and day 5 | |
| Secondary | levels of T lymphocytes (Treg) | From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies | between Day 7 and day 9 | |
| Secondary | dosage of cytokines | Day 1 | ||
| Secondary | dosage of cytokines | between Day 3 and day 5 | ||
| Secondary | dosage of cytokines | between Day 7 and day 9 | ||
| Secondary | Number of nosocomial infections | up to Day 30 | ||
| Secondary | Type of nosocomial infections | bacteremia, ventilator-associated pneumonia, urinary tract infection, other sites. | up to Day 30 | |
| Secondary | Mortality | up to Day 30 | ||
| Secondary | Length of vasoactive treatments | up to Day 30 |