Early Severe Illness TrAnslational BioLogy InformaticS in Humans

NCT05591924 | Recruiting

• 1 other identifier: 12145
• Study Type: observational
• Target: 1,000
• Locations: 1 country
• Sites: 1

Brief Summary

Advanced stages of the response to life-threatening infection, severe trauma, or other physiological insults often lead to exhaustion of the homeostatic mechanisms that sustain normal blood pressure and oxygenation. These syndromic presentations often meet the diagnostic criteria of sepsis and/or the acute respiratory distress syndrome (ARDS), the two most common syndromes encountered in the intensive care unit (ICU). Although critical illness syndromes, such as sepsis and ARDS, have separate clinical definitions, they often overlap clinically and share several common injury mechanisms. Moreover, there are no specific therapies for critically ill patients, and as a consequence, approximately 1 in 4 patients admitted to the ICU will not survive. The purpose of this observational study is to identify early patient biologic factors that are present at the time of ICU admission that will help diagnose critical illness syndromes earlier, identify who could benefit most from specific therapies, and enable the discovery of new treatments for syndromes such as sepsis and ARDS.

Conditions

Sepsis; ARDS; Critical Illness; Neurocognitive Dysfunction; Shock, Septic; Ventilator Associated Pneumonia; Immune Suppression; Inflammation; SIRS

Keywords

Critical Care; Sepsis; ARDS; Inflammation; Immune responses; Neurocognition; Critical illness; Translational Biology

Outcome Measures

Primary Outcomes (8)

• Risk of developing nosocomial infections during ICU admission

  Development of any of the following: Ventilator Associated Pneumonia, Central Line Infections, Clostridium difficile-Associated Diarrhea, Blood stream infections

  Assessed daily until discharge from ICU, through study completion, an average of 1 year

• Severity of illness measured by APACHE score

  APACHE

  At the time of ICU admission

• Severity of illness measured by SOFA score

  SOFA

  At the time of ICU admission

• Severity of illness measured by MODS score

  MODS

  At the time of ICU admission

• Change in severity of illness measured by APACHE score

  APACHE

  From the time of ICU admission, assessed daily until death or discharge from ICU, up to 12 months

• Change in severity of illness measured by SOFA score

  SOFA

  From the time of ICU admission, assessed daily until death or discharge from ICU, up to 12 months

• Change in severity of illness measured by MODS score

  MODS

  From the time of ICU admission, assessed daily until death or discharge from ICU, up to 12 months

• Hospital disposition

  Survival, death

  Determined at the time of discharge from the hospital, through study completion, an average of 1 year

Secondary Outcomes (2)

• Neurocognitive dysfunction

  1, 6, and 12 months after ICU discharge

• Physiological outcomes

  0, 24, 48, and 72 hours after ICU admission

Study Arms (2)

ESTABLISH

Adults over 18 years of age admitted to the ICU within 48 hours and whose presentation to the Emergency Department was within 72h of ICU admission.

Procedure: Phelebotomy; Procedure: Broncheoalveolar Lavage; Procedure: Tracheal Aspirate; Procedure: Rectal Swab

Healthy Controls

Adults over 18 years of age with no infectious symptoms, interaction with the health care system, or antimicrobial use in the past 14 days and no history of immunosuppression.

Procedure: Phelebotomy

Interventions

Phelebotomy PROCEDURE

Collection of 10mL of heparin anticoagulated blood, 10mL of EDTA anticoagulated blood, and 3mL of blood in a PAX gene tube

ESTABLISH; Healthy Controls

Broncheoalveolar Lavage PROCEDURE

Bronchioalveolar lavage fluid (BALF) samples will be obtained from participants who are mechanically ventilated, and a bronchoscopy is indicated as part of routine clinical care. The BALF will be collected by a qualified ICU physician using standard clinical practice. Briefly, patients will receive appropriate sedation and analgesia, a flexible video-bronchoscope will be inserted into the patient's airway, and bronchial segments will be identified. The bronchoscope will be wedged in the most appropriate lung segment and 40-100mL of sterile normal saline (NS) as clinically indicated, will be injected into the bronchoscope port with using a 50mL syringe. Next, the instilled NS (i.e.: lavage fluid) will be collected in a sterile container using gentle suction. The BALF will then be partitioned and sent to clinical laboratories, and the remaining BALF (10-20mL) will be used in the ESTABLISH research study.

ESTABLISH

Tracheal Aspirate PROCEDURE

Tracheal Aspirate (TA) will be obtained from participants who have an endotracheal tube or a tracheostomy in situ at the time of ICU admission through out the ICU admission on the study days, as long as distal airway access is available.

ESTABLISH

Rectal Swab PROCEDURE

A Rectal will be obtained at the time of ICU admission and on all study days during the ICU admission

ESTABLISH

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Critically ill adults with early critical illness

You may qualify if:

• Age ≥18 years old
• ≤48h since ICU admission
• ICU admission within 72h of presentation to the emergency department (ER)
• Clinical critical illness suspected on the basis of any one of the following:
• Altered mental status (GCS\<15)
• Cardiovascular collapse (presence of any: Heart rate \>90, systolic blood pressure \<90, presence of vasopressors, lactate \>2.0)
• Respiratory collapse (presence of any: respiratory rate \>20, PaCO₂ \<32 mm Hg, supplemental oxygen, invasive or non-invasive ventilation)
• Suspected severe infection (presence of any: temperature \>38°C or \<36°C, white blood cell (WBC) count \>12,000/mm³ or \<4,000/mm³, presence of 1 or more antibiotics at the time of ICU admission)

You may not qualify if:

• Age \<18 years old
• \>72h since ICU admission
• Admission to ICU in patients \>72h after the presentation to the ER
• No evidence of critical illness (ICU admission due to bed-spacing)

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead
• London Health Sciences Centre: collaborator
• Western University, Canada: collaborator
• Western University: collaborator

Study Sites (1)

Aleks Leligdowicz

London, Ontario, N6A 3K7, Canada

RECRUITING

Related Publications (8)

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  PMID: 9246838 BACKGROUND

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  PMID: 8617180 BACKGROUND

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  PMID: 9783171 BACKGROUND

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  PMID: 8534611 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

EDTA anticoagulated blood Heparin anticoagulated blood PAX gene tube Broncheoalveolar lavage fluid (BALF)

MeSH Terms

Conditions

Sepsis; Critical Illness; Cognition Disorders; Shock, Septic; Pneumonia, Ventilator-Associated; Inflammation

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes; Neurocognitive Disorders; Mental Disorders; Shock; Healthcare-Associated Pneumonia; Cross Infection; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease

Study Officials

• Aleks Leligdowicz, MD PhD

  Western University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Aleks Leligdowicz, MD PhD

CONTACT

519-661-2111; aleligdo@uwo.ca

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 24 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinician Scientist

Study Record Dates

• First Submitted: October 5, 2022
• First Posted: October 24, 2022
• Study Start: April 26, 2024
• Primary Completion (Estimated): December 31, 2034
• Study Completion (Estimated): December 31, 2034
• Last Updated: October 6, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Access Criteria: Collaborating researchers must be approved by the Lawson ethics board and/or the Western University HSREB.

Locations

CA (1)