Role of RNA Metabolism Alterations in Persistent Immune Dysfunction After Sepsis (SEPSI-splice)

Rôle Des Altérations Du Métabolisme De L'ARN Dans La Persistance Des Perturbations Immunitaires Au Décours Du Sepsis

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Sepsis

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.

• Study Type: Observational
• Enrollment (Estimated): 290

Contacts and Locations

• Study Contact: Name: Fabrice Uhel; Phone Number: 01 47 60 61 93; Email: fabrice.uhel@aphp.fr

Study Locations

• France
  • Colombes, France
    • Anesthésie
  • Colombes, France
    • Médecine Intensive Réanimation -Hôpital Louis Mourier

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Adult patients hospitalized in the ICU at Louis Mourier Hospital with either sepsis according to SEPSIS 3.0 criteria or a severe non-infectious condition. The study also includes a healthy ambulatory control group without infection.

Description

- 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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Septic Patients; Adult ICU patients hospitalized with sepsis according to SEPSIS 3.0 definitions. Inclusion criteria: age ≥ 18 years, suspected or documented infection, and SOFA score ≥ 2. No specific intervention; observational study collecting clinical and biological data including leukocyte transcriptome analyses.
Critically Ill Non-Septic Patients; Adult ICU patients hospitalized with severe non-infectious conditions, without infection. Inclusion criteria: age ≥ 18 years, SOFA score ≥ 2. No specific intervention; observational study collecting clinical and biological data including leukocyte transcriptome analyses.
Control Patients; Ambulatory adult patients (not hospitalized) without infection at the time of consultation. Inclusion criteria: age ≥ 18 years. No specific intervention; blood samples will be collected for transcriptome and immunomonitoring analyses.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Longitudinal leukocyte transcriptomic endotype classification	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.	From Day 1 to Month 12 after sepsis onset

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alternative splicing events in monocytes	Differential splice variant expression in circulating monocytes, measured by RNA sequencing over time in sepsis and control patients.	From Day 1 to Month 12 after sepsis onset
ICU length of stay	Length of ICU stay, measured in days from ICU admission to ICU discharge.	From ICU admission to ICU discharge
ICU mortality	All-cause mortality during ICU stay, reported as % of patients.	From ICU admission to ICU discharge
Nosocomial infections during ICU stay	Percentage of patients with ≥1 nosocomial infection during ICU stay.	From ICU admission to ICU discharge
Rehospitalizations within 12 months	Number of rehospitalizations for any cause within 12 months post-ICU discharge.	From ICU discharge to 12 months after sepsis diagnosis
New infectious episodes within 12 months	Percentage of patients with ≥1 new infectious episode within 12 months post-ICU discharge.	From ICU discharge to 12 months after sepsis diagnosis
Cardiovascular events within 12 months	Percentage of patients with ≥1 cardiovascular event (MI, stroke, heart failure) within 12 months post-ICU discharge.	From ICU discharge to 12 months after sepsis diagnosis
Incidence of clinical complications by longitudinal transcriptomic endotype	Percentage of patients experiencing ≥1 predefined clinical complication according to longitudinal transcriptomic endotype membership.	From Day 1 to Month 12 after sepsis onset
Genetic variants associated with longitudinal transcriptomic endotypes	Frequency of selected genetic polymorphisms associated with longitudinal transcriptomic endotype membership, assessed using genome-wide genotyping arrays.	From Day 1 to Month 12 after sepsis onset

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: January 27, 2026
• First Submitted That Met QC Criteria: February 11, 2026
• First Posted (Actual): February 18, 2026

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 25, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Sepsis; Leukocytes; Transcriptomics; Acute phase; Endotypes; Convalescence; Molecular trajectories; Recovery phase
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathological Conditions, Signs and Symptoms; Sepsis; Convalescence
• Other Study ID Numbers: APHP251573; 2025-A02505-44 (Registry Identifier: IDRCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No