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REAnimation Low Immune Status Markers (REALISM)

14. september 2018 oppdatert av: 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.

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Studietype

Intervensjonell

Registrering (Faktiske)

552

Fase

  • Ikke aktuelt

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

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

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

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

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Diagnostisk
  • Tildeling: N/A
  • Intervensjonsmodell: Enkeltgruppeoppdrag
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Blood sampling
Blood sampling will be performed in all patients and healthy volunteers
Biologisk: Blood sampling
Specific Blood sampling will be performed in patients and healthy volunteers

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Percentage of patients meeting the definition of of injury-induced-immunosuppression
Tidsramme: 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

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Proportion of patients with a deficiency of the innate or adaptive immunity
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Hospices Civils de Lyon

Samarbeidspartnere

Sanofi
Bioaster
BioMérieux

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

11. desember 2015

Primær fullføring (Faktiske)

27. juni 2018

Studiet fullført (Faktiske)

27. juni 2018

Datoer for studieregistrering

Først innsendt

18. desember 2015

Først innsendt som oppfylte QC-kriteriene

18. desember 2015

Først lagt ut (Anslag)

23. desember 2015

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

17. september 2018

Siste oppdatering sendt inn som oppfylte QC-kriteriene

14. september 2018

Sist bekreftet

1. september 2018

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • 69HCL15_0379
  • 2015-A01293-46 (Annen identifikator: ID-RCB)

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

Nei

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Nei

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

produkt produsert i og eksportert fra USA

Nei

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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