Molecular Subtype-Specific Mechanisms and Therapeutic Strategies in Sepsis (MENDSEP)

Sepsis is a complex syndrome that causes lethal organ dysfunction due to an abnormal host response to infection. No drug specifically targeting sepsis has been approved. The heterogeneity in sepsis pathophysiology hinders the identification of patients who would benefit, or be harmed, from specific therapeutic interventions. Recent clinical genomics studies have shown that sepsis patients can be stratified as molecular subtypes, or subclasses, with clinical implications. Classifying sepsis patients as molecular subtypes revealed that a poor prognosis subtype was characterized by immunosuppression and septic shock. Therefore, it has become essential to identify patients who may benefit from or be adversely affected by specific treatments, thereby identifying bona fide treatable traits or endotypes. The goal of this study is to assist the physician at the bedside in tailoring the treatment of an individual patient suffering from sepsis by generating rapid molecular information about immune status.

Study Overview

• Status: Recruiting
• Conditions: Sepsis; Septic Shock
• Intervention / Treatment: Diagnostic test: Blood transcriptomics and BAL protein profiling

• Study Type: Observational
• Enrollment (Estimated): 460

Contacts and Locations

• Study Contact: Name: Brendon P. Scicluna, Ph.D.; Phone Number: +35623403869; Email: brendon.scicluna@um.edu.mt
• Study Contact Backup: Name: Stephen C. Sciberras, M.D.; Phone Number: +35625450000; Email: stephen.sciberras@gov.mt

Study Locations

• Malta
  • Imsida, Malta, MSD2080
    • Recruiting
    • Mater Dei hospital, Intensive Therapy Unit
    • Contact: Stephen Sciberras, MD; Phone Number: +35625450000; Email: stephen.sciberras@gov.mt
    • Contact: Godfrey Azzopardi, MD; Phone Number: +35625450000; Email: godfrey.a.azzopardi@gov.mt
    • Principal Investigator: Brendon P. Scicluna, Ph.D.

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

All-cause sepsis, non-infectious critical illness, and control participants

Description

Inclusion criteria:

• Age ≥ 18 years
• Consent card signed

Exclusion criteria:

• Consent card not signed
• Pregnancy
• Prisoners
• Elective cardiac surgery patients with an uncomplicated stay.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Sepsis (all-cause); Suspected infection accompanied by organ dysfunction identified as a total SOFA score ≥ 2 points diagnosed within 24 hours after ITU admission. Definition in line with the Sepsis-3 criteria.
Non-infectious critical illness; Patients admitted to the ITU with non-infectious etiologies, including trauma.
Control subjects; Age-, sex-, and comorbidity-matched participants from the community or long term care facility

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Molecular subtype assignments	Molecular subtype classification of sepsis patients using a consensus transcriptomic subtype model	Through study completion, an average of 2 year
Molecular information about the host response in patients with sepsis	Measurement of soluble mediators of host immune responses, including inflammation, coagulation, endothelial function	Through study completion, an average of 2 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival	Assessment of survival	3 years

Collaborators and Investigators

• Sponsor: Mater Dei Hospital, Malta
• Collaborators: University of Malta

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2023
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): December 30, 2028

Study Registration Dates

• First Submitted: February 22, 2024
• First Submitted That Met QC Criteria: February 29, 2024
• First Posted (Actual): March 1, 2024

Study Record Updates

• Last Update Posted (Actual): July 16, 2025
• Last Update Submitted That Met QC Criteria: July 11, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia
• Other Study ID Numbers: SINO-MALTA-2024-40; ESICM-22

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
• product manufactured in and exported from the U.S.: No