Systems Analysis of Antigen Presenting Cells in Human Sepsis

Sepsis Clinical Trial

— DENDRISEPSIS  

Official title:

Systems Analysis of Antigen Presenting Cells in Human Sepsis.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03788772
• Other study ID #: APHP180016
• Secondary ID: 2018-A01934-51
• Status: Recruiting
• Phase: N/A
• Start date: July 15, 2019
• Est. completion date: July 15, 2022

Study information

• Verified date: July 2019
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Frédéric PENE, MD PhD
• Phone: +33 1 58 41 46 77
• Email: frederic.pene[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: July 15, 2022
• Est. primary completion date: July 15, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Circulatory Failure
• Sepsis
• Shock
• Toxemia

Intervention

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

Locations

Country	Name	City	State
France	Cochin Hospital, AP-HP	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ICU-acquired infections (nosocomial infections)	Infections not present at the time of ICU admission and diagnosed at least after 48 hours in the ICU	up to 3 months after the inclusion
Secondary	In-hospital death	date of death	up to 3 months after the inclusion