Sepsis
Conditions
Keywords
Sepsis, Endotypes, Molecular trajectories, Transcriptomics, Leukocytes, Acute phase, Recovery phase, Convalescence
Brief summary
This study includes adult ICU patients with sepsis (according to SEPSIS 3.0) or critically ill non-septic patients with severe non-infectious conditions at Louis Mourier Hospital. It is a prospective multicentre observational study aiming to describe leukocyte transcriptome changes and molecular trajectories (endotypes) during the acute, recovery, and convalescence phases of sepsis. A total of 290 participants will be included: 200 septic patients, 50 critically ill non-septic patients, and 40 control participants.
Detailed description
The study will be a prospective, multicentre, observational study including adult ICU patients hospitalized with sepsis (according to SEPSIS 3.0 definitions) or critically ill non-septic patients with severe non-infectious conditions at Louis Mourier Hospital. Participants will be assigned to one of three groups: * Septic patients group: 200 patients with suspected or documented infection and a SOFA score ≥2. * Critically ill non-septic patients group: 50 patients without infection and a SOFA score ≥2. * Control group: 40 ambulatory participants without infection, matched for age and sex. Blood samples for transcriptome and immunomonitoring analyses will be collected at predefined time points during ICU stay and post-ICU follow-up (J1, J3, J7, J14, M3, M6, M12). Routine clinical and laboratory parameters will also be recorded. The primary objective is to describe longitudinal molecular trajectories (endotypes) of circulating leukocytes over the natural course of sepsis. The primary endpoint is the identification of molecular endotypes from sequential transcriptome analyses. Secondary analyses will compare molecular profiles between septic and non-septic patients, evaluate the effects of alternative splicing on the cellular proteome, and correlate endotypes with clinical outcomes during ICU stay and up to 12 months post-inclusion. Bioinformatic methods (JLCMM, KmL) and pathway analysis (Ingenuity Pathway Analysis, Qiagen) will be used to identify patient groups with similar molecular profiles over time.
Interventions
None listed
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
Inclusion criteria
\- Septic patients group: Age ≥ 18 years Hospitalized in Intensive Care Medicine Suspected or confirmed infection SOFA score ≥ 2 \- Critically ill non-septic patients group: Age ≥ 18 years Hospitalized in Intensive Care Medicine No infection (neither suspected nor confirmed) SOFA score ≥ 2 \- Healthy control group Age ≥ 18 years Ambulatory patient (not hospitalized) No infection at the time of consultation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Longitudinal leukocyte transcriptomic endotype classification | From Day 1 to Month 12 after sepsis onset | Classification of patients into longitudinal leukocyte transcriptomic endotypes based on sequential circulating leukocyte RNA sequencing. Endotype membership will be determined using transcriptomic profiling and reported as categorical group assignment over time, including comparison with critically ill non-infected control patients. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Alternative splicing events in monocytes | From Day 1 to Month 12 after sepsis onset | Differential splice variant expression in circulating monocytes, measured by RNA sequencing over time in sepsis and control patients. |
| ICU length of stay | From ICU admission to ICU discharge | Length of ICU stay, measured in days from ICU admission to ICU discharge. |
| ICU mortality | From ICU admission to ICU discharge | All-cause mortality during ICU stay, reported as % of patients. |
| Nosocomial infections during ICU stay | From ICU admission to ICU discharge | Percentage of patients with ≥1 nosocomial infection during ICU stay. |
| Rehospitalizations within 12 months | From ICU discharge to 12 months after sepsis diagnosis | Number of rehospitalizations for any cause within 12 months post-ICU discharge. |
| New infectious episodes within 12 months | From ICU discharge to 12 months after sepsis diagnosis | Percentage of patients with ≥1 new infectious episode within 12 months post-ICU discharge. |
| Cardiovascular events within 12 months | From ICU discharge to 12 months after sepsis diagnosis | Percentage of patients with ≥1 cardiovascular event (MI, stroke, heart failure) within 12 months post-ICU discharge. |
| Incidence of clinical complications by longitudinal transcriptomic endotype | From Day 1 to Month 12 after sepsis onset | Percentage of patients experiencing ≥1 predefined clinical complication according to longitudinal transcriptomic endotype membership. |
| Genetic variants associated with longitudinal transcriptomic endotypes | From Day 1 to Month 12 after sepsis onset | Frequency of selected genetic polymorphisms associated with longitudinal transcriptomic endotype membership, assessed using genome-wide genotyping arrays. |
Countries
France
Contacts
CONTACTFabrice Uhel
Outcome results
None listed