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

Primary Purpose

Sepsis, Acute Circulatory Failure

Status
Unknown status
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Multiple blood sampling
Simple blood sampling
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Sepsis focused on measuring dendritic cell, sepsis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Cochin Hospital, AP-HPRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Adults patients hospitalized in ICU

Arm Description

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)

Outcomes

Primary Outcome Measures

ICU-acquired infections (nosocomial infections)
Infections not present at the time of ICU admission and diagnosed at least after 48 hours in the ICU

Secondary Outcome Measures

In-hospital death
date of death

Full Information

First Posted
December 20, 2018
Last Updated
December 2, 2019
Sponsor
Assistance Publique - Hôpitaux de Paris
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1. Study Identification

Unique Protocol Identification Number
NCT03788772
Brief Title
Systems Analysis of Antigen Presenting Cells in Human Sepsis
Acronym
DENDRISEPSIS
Official Title
Systems Analysis of Antigen Presenting Cells in Human Sepsis.
Study Type
Interventional

2. Study Status

Record Verification Date
July 2019
Overall Recruitment Status
Unknown status
Study Start Date
July 15, 2019 (Actual)
Primary Completion Date
July 15, 2022 (Anticipated)
Study Completion Date
July 15, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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: Systematic description and phenotypic analysis of circulating APC subsets in sepsis Association of APC subsets distribution, phenotype and function with severe sepsis physiopathology and relevant clinical outcomes (ICU-acquired infections and death) 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sepsis, Acute Circulatory Failure
Keywords
dendritic cell, sepsis

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
160 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Adults patients hospitalized in ICU
Arm Type
Experimental
Arm Description
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)
Intervention Type
Other
Intervention Name(s)
Multiple blood sampling
Intervention Description
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)
Intervention Type
Other
Intervention Name(s)
Simple blood sampling
Intervention Description
Healthy controls (blood donors and patients undergoing elective cataract surgery) will be subjected to one single blood sample of 20 mL.
Primary Outcome Measure Information:
Title
ICU-acquired infections (nosocomial infections)
Description
Infections not present at the time of ICU admission and diagnosed at least after 48 hours in the ICU
Time Frame
up to 3 months after the inclusion
Secondary Outcome Measure Information:
Title
In-hospital death
Description
date of death
Time Frame
up to 3 months after the inclusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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 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. Healthy controls: Blood donors Patients undergoing elective cataract surgery Exclusion Criteria: 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. 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Frédéric PENE, MD PhD
Phone
+33 1 58 41 46 77
Email
frederic.pene@aphp.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Frédéric PENE, MD PhD
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Vassili SOUMELIS, MD PhD
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Study Director
Facility Information:
Facility Name
Cochin Hospital, AP-HP
City
Paris
ZIP/Postal Code
75014
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Frédéric PENE, MD PhD
Phone
+33 1 58 41 46 77
Email
frederic.pene@aphp.fr

12. IPD Sharing Statement

Plan to Share IPD
No

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Systems Analysis of Antigen Presenting Cells in Human Sepsis

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