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REAnimation Low Immune Status Markers (REALISM)

14 september 2018 bijgewerkt door: Hospices Civils de Lyon

The fact that sepsis disrupts immune system homeostasis by inducing an initial cytokine storm, that participates to occurrence of organ failures and early death, followed by a compensatory anti-inflammatory response leading to immunosuppression, is now well established. This immunomodulating response results in a higher risk of secondary infections and is associated to 2/3 of deaths related to septic shocks. Follow up of patients' immune status with time is crucial to guide therapy management. Objective of REALISM project is to demonstrate existence of this immunosuppression phase, by providing strong epidemiologic data for septic shock patients, but also by extension to other situations of inflammatory aggressions like severe severe trauma or burns, or major surgery. This project will provide tools to predict occurrence of secondary infections and guide patient management by comparing innovating immunomonitoring tools to reference tests non already adapted to a routine patient management.

Targeted populations are adult patients hospitalized for septic shock, severe trauma (including severe burn) or major surgery and healthy volunteers, whom blood samples will serve to validate reference intervals of the two reference tests.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Studietype

Ingrijpend

Inschrijving (Werkelijk)

552

Fase

  • Niet toepasbaar

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Frankrijk
      • LYON cedex 03, Frankrijk, 69437
        • Service d'Anesthésie Réanimation - Hôpital Edouard Herriot

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

Inclusion criteria for patients

  • Patient or next of kin having been informed of the conditions of the study and having signed the informed consent form

  • Patient hospitalized for :

    • Septic shock
    • Severe trauma (including severe burn)
    • Major surgery

Inclusion criteria for healthy volunteers

  • Normal clinical examination
  • Signed informed consent form
  • Person with social security insurance

Exclusion criteria for patients

  • Patient with severe neutropenia (neutrophil count <0.5 g/l)
  • Patients receiving immunosuppressive therapy
  • Patients receiving corticosteroids (IV or Per os)
  • Use of therapeutic antibodies
  • Hematological disease under treatment, or treated within 5 years before inclusion
  • End of chemotherapy within the 6 months prior to inclusion
  • Patient with innate or acquired immune deficiency (for example severe combined immunodeficiency, HIV or AIDS, any stage)
  • Patients for whom a care limitation was pronounced at time of enrolment
  • Anticipated length of stay before discharge from the ICU is estimated at less than 48 hours
  • Participation in an intervention study
  • Extra-corporeal circulation in the month preceding inclusion in case of cardiac surgery
  • Pregnant or breastfeeding women
  • Patient with no social security insurance, with restricted liberty or under legal protection

Exclusion criteria for healthy volunteers

  • Person with an infectious syndrome during the last 90 days
  • Extreme physical stress within the last week

  • Person having received within the last 90 days, a treatment based on

    • Antivirals
    • Antibiotics
    • Antiparasitics
    • Antifungics
  • Person having received within the last 15 days, a treatment based on non-steroidal anti-inflammatory drugs (NSAIDs)

  • Person having received within the last 24 months, a treatment based on

    • Immunosuppressive therapy
    • Corticosteroids (IV or Per os)
    • Therapeutic antibodies
    • Chemotherapy

  • History of :

    • innate or acquired immune deficiency
    • Hematological disease
    • Solid tumor
    • Severe chronic disease
    • Surgery or hospitalization within the last 2 years
    • Pregnancy within the last year
  • Participation to a phase I clinical assay during the last year
  • Pregnant or breastfeeding women
  • Person with restricted liberty or under legal protection

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Diagnostisch
  • Toewijzing: NVT
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Blood sampling
Blood sampling will be performed in all patients and healthy volunteers
Biologisch: Blood sampling
Specific Blood sampling will be performed in patients and healthy volunteers

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Percentage of patients meeting the definition of of injury-induced-immunosuppression
Tijdsspanne: Up to 2 months after injury
The immunosuppression status will be determined from two immunological reference tests: (1) lymphocyte proliferation in response to ex vivo T cell stimulation (adaptive immunity) (Poujol et al., 2014) and (2) the production of tumor necrosis factor (TNF) by monocytes in response to ex vivo stimulation by lipopolysaccharide (LPS) (innate immunity) (Duffy et al., 2014). The values measured will be defined as normal or abnormal, depending on whether they are within reference intervals (RI) derived from an independent set of healthy volunteers. For this purpose, the definition of immunosuppression will be: an abnormal result in at least one of the two "reference" tests (outside the reference intervals defining normal values), and on at least two consecutive samples. The same reference test must be abnormal in two successive samples examined for the patient to be considered immunosuppressed.
Up to 2 months after injury

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Proportion of patients with a deficiency of the innate or adaptive immunity
Tijdsspanne: Up to 2 months after injury

Intensity of the innate immune deficiency will be measured using the production of TNF by monocytes in response to ex vivo stimulation by LPS (Duffy et al., 2014). Intensity of the adaptive immune deficiency will be measured using the lymphocyte proliferation in response to ex vivo T cell stimulation (Poujol et al., 2014). The values measured will be defined as normal or abnormal, depending on whether they are within reference intervals derived from an independent set of healthy volunteers. We will describe for all groups of patients:

  • The proportion of patients with a deficiency of the innate immunity, defined by an abnormal TNF secretion test result after LPS stimulation, for at least two consecutive samples.
  • The proportion of patients with a deficiency of the adaptive immunity, defined by an abnormal lymphocyte proliferation, for at least two consecutive samples.
  • The proportion of patients with at least one abnormal test on Days 1, 3-4, 5-7, 13/18, 26/36 and 52/68
Up to 2 months after injury
Comparison of performance of the reference tests and new biomarkers for the diagnosis of immunosuppression
Tijdsspanne: Up to one week after injury
Reference tests being non-standardized and cumbersome to implement, and time to results being incompatible with clinical practice, the use of simpler and quicker tests, based on the use of new biomarkers, would allow the individualization of patient management based on the patient's immune status. One of the secondary objectives is to evaluate the performance of new biomarkers compared to the two reference tests to diagnose immunosuppression. Different types of markers and tests will be evaluated: Viral reactivation markers, host-response markers, immune functional assays, immunophenotyping.
Up to one week after injury
Correlation between the immunosuppression status and the incidence of healthcare-associated infections
Tijdsspanne: Up to 28 days after injury
To evaluate the association between the immunosuppression status as defined in primary objective and the occurrence of secondary infections related to healthcare, the association of the immunosuppression status upon the occurrence of secondary infection will be examined first, and secondly any possible association between the levels of each of the reference tests and the occurrence of secondary infections will be characterized. In this analysis, a secondary infection related to healthcare will be defined as an infection occurring after inclusion in the study, between inclusion and day 28.
Up to 28 days after injury
Correlation between immunosuppression and mortality
Tijdsspanne: Up to 90 days after injury
We will examine the association between immunosuppression (as defined in the primary objective) and in-hospital mortality. Association will be evaluated par measuring occurrence of mortality at days 14, 28, 60 and 90, in the different groups.
Up to 90 days after injury
Comparison of immune status before and after surgery in the population of surgical patients
Tijdsspanne: Up to 2 months after surgery
The possibility of taking a sample before surgical stress should allow measurements of the impact of the procedure on the host response, and especially on any subsequent onset of immunosuppression. Oncological pathologies and treatments implemented prior to surgery may also be associated with immunosuppression, and for this reason patients hospitalized for cancer surgery will be compared to those hospitalized for vascular surgery. Impact of surgery on immunosuppression will be measured by comparing immune status as defined by the reference tests, in the population of surgical patients before and after surgery.
Up to 2 months after surgery

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Hospices Civils de Lyon

Medewerkers

Sanofi
Bioaster
BioMérieux

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

11 december 2015

Primaire voltooiing (Werkelijk)

27 juni 2018

Studie voltooiing (Werkelijk)

27 juni 2018

Studieregistratiedata

Eerst ingediend

18 december 2015

Eerst ingediend dat voldeed aan de QC-criteria

18 december 2015

Eerst geplaatst (Schatting)

23 december 2015

Updates van studierecords

Laatste update geplaatst (Werkelijk)

17 september 2018

Laatste update ingediend die voldeed aan QC-criteria

14 september 2018

Laatst geverifieerd

1 september 2018

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • 69HCL15_0379
  • 2015-A01293-46 (Andere identificatie: ID-RCB)

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

Nee

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

product vervaardigd in en geëxporteerd uit de V.S.

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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