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Systems Analysis of Antigen Presenting Cells in Human Sepsis (DENDRISEPSIS)

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ClinicalTrials.gov Identifier: NCT03788772
Recruitment Status : Recruiting
First Posted : December 28, 2018
Last Update Posted : December 3, 2019
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:

Sepsis is a common life-threatening inflammatory response to infection and is the leading cause of death in the intensive care unit. Septic patients exhibit a complex immunosuppressive response affecting both innate and adaptive components of immunity, with a possible link to nosocomial infections. However, the molecular and cellular mechanisms resulting in secondary immunosuppression remain poorly understood, but may involve the antigen-presenting cells (APC, including dendritic cells and monocytes/macrophages) that link innate and adaptive immunity. Furthermore, the increasing phenotypic and functional heterogeneity of APC subsets raise the question of their respective role in sepsis. We propose to address the pathophysiologal role of APC using systems biology approaches in human sepsis.

The objective is to go from low- to high-resolution analysis of APC subset diversity and underlying molecular and functional features in sepsis. The global objective will be reached through:

  1. Systematic description and phenotypic analysis of circulating APC subsets in sepsis
  2. Association of APC subsets distribution, phenotype and function with severe sepsis physiopathology and relevant clinical outcomes (ICU-acquired infections and death)
  3. High-resolution molecular profiling of circulating APC subsets using population level and single cell RNAseq.

To this aim, the investigator designed a prospective interventional study in order to collect blood samples at significant time points in patients with sepsis or septic shock (the population of interest) and relevant control subjects, either critically ill patients with non-septic acute circulatory failure or age-matched healthy subjects. The study's intervention is limited to additional blood samples. The risks and constraints are related to additional blood samples (maximum 120mL), which will be performed either from an arterial catheter when present in ICU patients, or from a venous puncture for patients without arterial catheters and for healthy volunteers.


Condition or disease Intervention/treatment Phase
Sepsis Acute Circulatory Failure Other: Multiple blood sampling Other: Simple blood sampling Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Systems Analysis of Antigen Presenting Cells in Human Sepsis.
Actual Study Start Date : July 15, 2019
Estimated Primary Completion Date : July 15, 2022
Estimated Study Completion Date : July 15, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sepsis

Arm Intervention/treatment
Experimental: Adults patients hospitalized in ICU
Adult patients hospitalized in the intensive care unit (ICU) for severe infections (sepsis and septic shock) or or non-septic shock (cardiogenic or hemorrhagic shock)
Other: Multiple blood sampling
ICU septic and non-septic patients will be subjected to repeated blood samples at the following time-points: ICU admission, day 4/5, ICU and hospital discharge, 3 months. Patients exhibiting ICU-acquired infection will also be sampled at the time of diagnosis (up to 6 additional blood samples of 20 mL within 3 months = 120mL)

Other: Simple blood sampling
Healthy controls (blood donors and patients undergoing elective cataract surgery) will be subjected to one single blood sample of 20 mL.




Primary Outcome Measures :
  1. ICU-acquired infections (nosocomial infections) [ Time Frame: up to 3 months after the inclusion ]
    Infections not present at the time of ICU admission and diagnosed at least after 48 hours in the ICU


Secondary Outcome Measures :
  1. In-hospital death [ Time Frame: up to 3 months after the inclusion ]
    date of death



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. ICU patients with severe infections (Sepsis-3 definitions):

    clinically or microbiologically documented infection and organ dysfunction graded as follows:

    • Sepsis: increase in the Sequential Organ Failure Assessment (SOFA) score of 2 points or more.
    • Septic shock: vasopressor requirement to maintain a mean arterial pressure ≥ 65mmHg and serum lactate level > 2 mmol/L in the absence of hypovolemia
  2. ICU patients with non-septic acute circulatory failure:

    • Cardiogenic shock: left ventricle systolic dysfunction (echocardiographic left ventricular ejection fraction < 45%) and the need of vasopressor (norepinephrine at any dose and inotropic support (dobutamine ≥ 5 µg/kg/min or epinephrine at any dose) in the absence of patent infection.
    • Severe hemorrhage: hypotension with acute blood loss requiring transfusion of at least four packed red cells within 24h and vasopressor support by norepinephrine or epinephrine at any dose.
  3. Healthy controls:

    • Blood donors
    • Patients undergoing elective cataract surgery

Exclusion Criteria:

  1. All ICU patients

    • hematological malignancy (or significant history of bone marrow disease),
    • HIV infection at any stage,
    • any immunosuppressive drugs including corticosteroids ≥ 0.5 mg/kg equivalent prednisone per day for more 7 days,
    • anticancer chemotherapy or chemotherapy received during the last three months before inclusion
    • bone marrow or solid organ transplantation,
    • leucopenia (<1000/mm3) excepted if due to sepsis,
    • pregnancy
    • do-not-resuscitate order at ICU admission
    • patients under legal protection regimen.
  2. Healthy controls

    • history of inflammatory disease
    • hematological malignancy (or significant history of bone marrow disease),
    • HIV infection at any stage,
    • any immunosuppressive drugs including corticosteroids ≥ 0.5 mg/kg equivalent prednisone per day for more 7 days,
    • anticancer chemotherapy or immunotherapy received during the last three months before inclusion
    • bone marrow or solid organ transplantation,
    • pregnancy
    • infectious symptoms within the previous month
    • subjects under legal protection regimen

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03788772


Contacts
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Contact: Frédéric PENE, MD PhD +33 1 58 41 46 77 frederic.pene@aphp.fr

Locations
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France
Cochin Hospital, AP-HP Recruiting
Paris, France, 75014
Contact: Frédéric PENE, MD PhD    +33 1 58 41 46 77    frederic.pene@aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
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Principal Investigator: Frédéric PENE, MD PhD Assistance Publique - Hôpitaux de Paris
Study Director: Vassili SOUMELIS, MD PhD Assistance Publique - Hôpitaux de Paris

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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT03788772     History of Changes
Other Study ID Numbers: APHP180016
2018-A01934-51 ( Other Identifier: ID-RCB )
First Posted: December 28, 2018    Key Record Dates
Last Update Posted: December 3, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
dendritic cell
sepsis
Additional relevant MeSH terms:
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Sepsis
Toxemia
Shock
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes