Clinical trial NCT04292431: Leukocyte MOrphology and CORticosteroids Response in SEPtic Patients (MOCORSEP)
Official title: Exploration of Variations in Leukocyte Morphological Parameters (MDW and CPD) Using the Beckman Coulter DxH900, Based on the Infectious Condition, Inflammatory State and Response to Corticosteroid Therapy in Septic Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Sepsis
Septic Shock
Sepsis Syndrome
Infection
Keywords: Leukocyte morphology
Corticosteroid
MDW
Cell population data
DxH900
Lead sponsor: Beckman Coulter, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Hôpital Raymond Poincaré
name: Saint-Louis Hospital, Paris, France
First posted: 2020-03-03
Enrollment: 175
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Non infected (n=50) Infection (n=50) Sepsis + SOFA \> 2 (n=25) Sepsis (SOFA \> 2) + vasopressors and lactate ≤ 2 mmol/L (n=25) Septic shock (SOFA \> 2 + vasopressor + lactate \> 2 mmol/L) (n=25)

Brief summary: Non-interventional, prospective, monocentric study on the exploration of leukocyte morphological parameters according to the infectious condition and response to corticosteroid therapy of septic patients.

Detailed description: Sepsis is a major public health issue, caused by an organ disorder related to an immune response not controlled by the infection.

Several randomized trials have shown that the combination of glucocorticoids and mineralocorticoids improves the survival rate of patients in septic shock. The optimal use of this therapeutic approach requires identifying the pro-inflammatory phase patients likely to respond to corticosteroid therapy.

Hyperactivation of immune cells is accompanied by morphological changes likely to be characterized by modern hematology instruments, particularly the DxH900 (Beckman Coulter). The DxH900 is able to use specific techniques to determine a significant number of morphological characteristics (CPD or Cell Population Data) for circulating leukocytes. Recently, one of these leukocyte morphological parameters, MDW (Monocyte Distribution Width), has been clinically approved for identifying septic patients or those at risk of developing sepsis. This MDW parameter currently has the CE IVD mark and is approved by the American FDA.

The aim of the study is to explore the hypothesis that leukocyte morphological parameters, including MDW, may constitute functional biomarkers of pro-inflammatory response and help to identify septic patients likely to optimally respond to a combination treatment of glucocorticoids and mineralocorticoids, and thus improve their chances of survival.

The proposed study is a non-interventional, prospective, monocentric cohort study to explore the variation of leukocyte morphological parameters measured on the DxH900 hematology analyzer according to the different infectious conditions of patients ranging from a known or suspected infection to septic shock versus non-infected control patients, and possibly based on the response. This observational cohort study will consist of patients with a known or suspected infection, sepsis or in septic shock on their date of admission into one of the medical or surgical departments and monitored up to day 7 of the hospital stay or on the date of discharge from the hospital, whichever occurs first.

Eligibility criteria: Inclusion Criteria:

* an infection (known or suspected)
* sepsis
* sepsis + vasopressor
* septic shock

  * responders to corticosteroid therapy
  * non-responders to corticosteroid therapy

Exclusion Criteria:

* Pregnant women
* Patients with onco-hematological diseases with the presence of blasts.

Primary outcomes:
measure: Leukocytes morphological parameters differs between patient's groups
timeFrame: 7 days
Secondary outcomes:
measure: Leukocytes morphological parameters preditcs inflammatory status
timeFrame: 7 days
measure: Leukocytes morphological parameters preditcs responce to corticosteroids treatments
timeFrame: 7 days
Other outcomes:
Locations:
city: Garches
country: France
facility: Hospital Raymond Poincaré
state: Paris
Study officials:
affiliation: Hospital Raymond Poincaré
name: Djillali Annane, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Raymond Poincaré
name: Pierre Moine, MD
role: STUDY_CHAIR
affiliation: Hospital Raymond Poincaré
name: Martin Rottman, MD
role: STUDY_CHAIR
affiliation: Hospital Saint Louis Lariboisière Fernand-Widal
name: Sylvie Chevret, MD
role: STUDY_CHAIR
References:
citation: Annane D, Renault A, Brun-Buisson C, Megarbane B, Quenot JP, Siami S, Cariou A, Forceville X, Schwebel C, Martin C, Timsit JF, Misset B, Ali Benali M, Colin G, Souweine B, Asehnoune K, Mercier E, Chimot L, Charpentier C, Francois B, Boulain T, Petitpas F, Constantin JM, Dhonneur G, Baudin F, Combes A, Bohe J, Loriferne JF, Amathieu R, Cook F, Slama M, Leroy O, Capellier G, Dargent A, Hissem T, Maxime V, Bellissant E; CRICS-TRIGGERSEP Network. Hydrocortisone plus Fludrocortisone for Adults with Septic Shock. N Engl J Med. 2018 Mar 1;378(9):809-818. doi: 10.1056/NEJMoa1705716.
citation: Annane D, Sebille V, Charpentier C, Bollaert PE, Francois B, Korach JM, Capellier G, Cohen Y, Azoulay E, Troche G, Chaumet-Riffaud P, Bellissant E. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002 Aug 21;288(7):862-71. doi: 10.1001/jama.288.7.862.
citation: Crouser ED, Parrillo JE, Seymour C, Angus DC, Bicking K, Tejidor L, Magari R, Careaga D, Williams J, Closser DR, Samoszuk M, Herren L, Robart E, Chaves F. Improved Early Detection of Sepsis in the ED With a Novel Monocyte Distribution Width Biomarker. Chest. 2017 Sep;152(3):518-526. doi: 10.1016/j.chest.2017.05.039. Epub 2017 Jun 15.
citation: Crouser ED, Parrillo JE, Seymour CW, Angus DC, Bicking K, Esguerra VG, Peck-Palmer OM, Magari RT, Julian MW, Kleven JM, Raj PJ, Procopio G, Careaga D, Tejidor L. Monocyte Distribution Width: A Novel Indicator of Sepsis-2 and Sepsis-3 in High-Risk Emergency Department Patients. Crit Care Med. 2019 Aug;47(8):1018-1025. doi: 10.1097/CCM.0000000000003799.