- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica NCT02848144
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.
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Tipo di studio
Iscrizione (Effettivo)
Fase
- Non applicabile
Contatti e Sedi
Luoghi di studio
-
-
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Lyon, Francia
- Hospices Civils De Lyon
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-
Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Scienza basilare
- Assegnazione: Non randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
---|---|
Altro: 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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Altro: 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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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
proportion of patients with a mHLA-DR level <30%
Lasso di tempo: up to Day 9
|
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.
Lasso di tempo: in the pre-operative period
|
mHLA-DR is measured by flow cytometry
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in the pre-operative period
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
total lymphocytes
Lasso di tempo: Day 1
|
From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies
|
Day 1
|
total lymphocytes
Lasso di tempo: between Day 3 and day 5
|
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
|
total lymphocytes
Lasso di tempo: between Day 7 and day 9
|
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
|
levels of CD4+
Lasso di tempo: Day 1
|
From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies
|
Day 1
|
levels of CD4+
Lasso di tempo: between Day 3 and day 5
|
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
|
levels of CD4+
Lasso di tempo: between Day 7 and day 9
|
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
|
levels of CD25+
Lasso di tempo: day 1
|
From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies
|
day 1
|
levels of CD25+
Lasso di tempo: between Day 3 and day 5
|
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
|
levels of CD25+
Lasso di tempo: between Day 7 and day 9
|
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
|
levels of T lymphocytes (Treg)
Lasso di tempo: Day 1
|
From the whole blood samples, each lymphocytes sub-populations are determined by flow-cytometry with addition of specific monoclonal antibodies
|
Day 1
|
levels of T lymphocytes (Treg)
Lasso di tempo: between Day 3 and day 5
|
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
|
levels of T lymphocytes (Treg)
Lasso di tempo: between Day 7 and day 9
|
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
|
dosage of cytokines
Lasso di tempo: Day 1
|
Day 1
|
|
dosage of cytokines
Lasso di tempo: between Day 3 and day 5
|
between Day 3 and day 5
|
|
dosage of cytokines
Lasso di tempo: between Day 7 and day 9
|
between Day 7 and day 9
|
|
Number of nosocomial infections
Lasso di tempo: up to Day 30
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up to Day 30
|
|
Type of nosocomial infections
Lasso di tempo: up to Day 30
|
bacteremia, ventilator-associated pneumonia, urinary tract infection, other sites.
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up to Day 30
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Mortality
Lasso di tempo: up to Day 30
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up to Day 30
|
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Length of vasoactive treatments
Lasso di tempo: up to Day 30
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up to Day 30
|
Collaboratori e investigatori
Sponsor
Investigatori
- Investigatore principale: Etienne JAVOUHEY, Hospices Civils De Lyon
Pubblicazioni e link utili
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- 69HCL16_0478
Piano per i dati dei singoli partecipanti (IPD)
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Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .
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