Molecular Endotype-Specific Dynamics of Lung Endothelial Barrier Integrity 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 endotypes, or subclasses, with important clinical implications. Classifying sepsis patients as molecular endotypes revealed that a poor prognosis endotype was characterized by immunosuppression and septic shock. Against this backdrop, the study hypothesis is that a poor prognosis for sepsis is defined by a molecular endotype reflecting impaired innate immune and endothelial barrier integrity in the primary anatomical site of infection.

Study Overview

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

• Study Type: Observational
• Enrollment (Estimated): 132

Contacts and Locations

• Study Contact: Name: Brendon Scicluna, Ph.D.; Phone Number: +35623401882; Email: brendon.scicluna@um.edu.mt
• Study Contact Backup: Name: Carmel Abela, M.D.; Phone Number: +35625450000; Email: carmel.c.abela@gov.mt

Study Locations

• Malta
  • Imsida, Malta, MSD2080
    • Recruiting
    • Mater Dei hospital, Intensive Care Unit
    • Contact: Carmel Abela; Phone Number: +35625450000; Email: carmel.c.abela@gov.mt

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Sepsis secondary to community- or hospital-acquired pneumonia

Description

Inclusion Criteria:

• Age ≥ 18 years
• Acute respiratory tract infection due to community- or hospital-acquired pneumonia

Exclusion Criteria:

• Consent card not signed
• Pregnancy
• Prisoners
• Aspiration pneumonitis
• Patients with ventilator-associated pneumonia

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient stratification as transcriptomic endotypes	Molecular endotype classification of sepsis patients secondary to pneumonia	Through study completion, an average of 1 year
Lung endothelial barrier integrity	Measurement of soluble mediators of endothelial function in bronchoalveolar lavage	Through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival	Assessment of survival	2 years

Collaborators and Investigators

• Sponsor: Mater Dei Hospital, Malta
• Collaborators: European Society of Intensive Care Medicine; University of Malta

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2023
• Primary Completion (Estimated): December 30, 2025
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

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

Study Record Updates

• Last Update Posted (Estimated): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

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: 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