SepsisESTABLISHNCT05591924
Early Severe Illness TrAnslational BioLogy InformaticS in Humans
An observational study of Sepsis and ARDS, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Sepsis, ARDS, Critical Illness
- What is being tested?
- Phelebotomy, Broncheoalveolar Lavage and Tracheal Aspirate
- Type of treatment
- Injection or infusion, Surgery or procedure
- How many people
- 1,000 participants
- Where
- 1 siteCanada
- Study dates
- 26 Apr 2024to 31 Dec 2034
- How long will I take part?
- 24 Months
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Critically ill adults with early critical illness
Who may be able to join
- 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)
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
Aleks Leligdowicz
London, Ontario, N6A 3K7
Aleks Leligdowicz, MD PhD, 519-661-2111 ext. 87241, aleks.leligdowicz@lhsc.on.ca
About this study
Official title: Prospective Observational Study of Biology of Critical Illness
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.
Read the detailed description
Background:
Critical illness syndromes, such as sepsis and ARDS, are associated with tremendous heterogeneity in patient predisposing risk factors, mechanisms of acute insult contributing to infection, presenting symptoms, response to therapies, as well as short and long-term outcomes. Since the first standardization of sepsis and ARDS definitions >30 years ago, significant insight into biological mechanisms contributing to critical illness syndromes have been made. However, there are many important unanswered questions that prevent accurate diagnosis, treatment, and prognosis of patients who present to the ICU with early symptoms consistent with critical illness.
Of the many gaps about the biology of sepsis and ARDS that remain unanswered, the following are particularly important: (1) what constitutes immune system dysregulation; (2) how the immune system response depends on interaction with the infecting pathogens; (3) what biologic traits distinguish other diagnoses that mimic these syndromes; (4) what are the mechanisms of genetic polymorphisms in patient outcomes. To address these questions and to improve our understanding of these complex and heterogenous syndromes, a multifaceted and collaborative approach is needed. This study will investigate the biology of early sepsis in critically ill patients by developing a longitudinal prospective observational cohort called Early Severe illness TrAnslational BioLogy InformaticS in Humans (ESTABLISH).
Specific objectives:
Objective 1: To study biologic mechanisms of immune system regulation during early critical illness. The main questions that will be addressed include: (1) how immune function at the time of admission and over the course of the ICU stay is related to clinical complications; (2) how anatomic compartmentalization of immune responses is associated with clinical complications; (3) how immune responses in different anatomic locations contribute to endothelial cell injury; (4) how macrophages contribute to distal organ injury and long-term clinical complications.
Objective 2: To characterize the host-pathogen interaction during early critical illness. The main question that will be addressed include: (1) how the microbial composition at the time of ICU admission affects the immune response; (2) how the change in host-pathogen interactions over time influence clinical complications.
Objective 3: To identify biologic traits that distinguish patients with early sepsis and ARDS from other critically ill patients. The main questions that will be addressed include: (1) are biological trains unique to sepsis and/or ARDS, or are they shared by other clinical diagnoses that mimic these syndromes?; (2) can accurately prognosticate clinically important short and long-term patient outcomes?; (3) are biologic traits associated with differential responses to therapies?
Objective 4: To study the molecular mechanisms of genetic polymorphisms associated with critical illness using induced pluripotent stem cells (iPSCs) derived from polymorphonuclear cells (PBMCs) from critically ill patients. The main questions that will be addressed include: (1) how do autologous iPSC-derived cell lineages interact with autologous plasma?; (2) how do iPSC-derived cell lineages respond to treatment with drugs related to genetic polymorphisms function?; (3) how do iPSC-derived lineages respond to treatment with drugs commonly used in the ICU?
Methods:
The ESTABLISH cohort will enroll patients within 48 hours of ICU admission who presented to the emergency department within 72 hours of ICU admission. Patients will be enrolled with deferred consent to enable the earliest possible collection of biological specimen. The biological specimen will include anticoagulated blood, a PAX gene tube, and a bronchioalveolar lavage fluid (BALF) sample (in mechanically ventilated patients, when bronchoscopy is clinically indicated) collected at the time of ICU admission (Day 0), and on 4 subsequent timepoints during the ICU admission (Days 1,3,7,14,21).
Data generated during ESTABLISH will be analyzed in batches on an ongoing, regular basis and will be objective-specific. Batch sample preparation and data analysis will minimize biological assay and methodological heterogeneity. Objective 1 and 2 data will be analyzed after enrollment of the first 50 patients, and every 50 patients after this. Objective 3 data will be analyzed after enrollment of the first 200 patients and every 200 patients after this.
- Conditions
- Sepsis, ARDS, Critical Illness, Neurocognitive Dysfunction, Shock, Septic, Ventilator Associated Pneumonia
- Being tested
- Phelebotomy, Broncheoalveolar Lavage, Tracheal Aspirate, Rectal Swab
- Keywords
- Critical Care, Sepsis, ARDS, Inflammation, Immune responses, Neurocognition, Critical illness, Translational Biology
- Medical subject headings
- Sepsis, Critical Illness, Cognition Disorders, Shock, Septic, Pneumonia, Ventilator-Associated, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PhelebotomyProcedure or surgery
Collection of 10mL of heparin anticoagulated blood, 10mL of EDTA anticoagulated blood, and 3mL of blood in a PAX gene tube
Broncheoalveolar LavageProcedure or surgery
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.
Tracheal AspirateProcedure or surgery
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.
Rectal SwabProcedure or surgery
A Rectal will be obtained at the time of ICU admission and on all study days during the ICU admission
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Procedure: Phelebotomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Assessed daily until discharge from ICU, through study completion, an average of 1 year
Severity of illness measured by APACHE score
APACHE
Measured: At the time of ICU admission
Severity of illness measured by SOFA score
SOFA
Measured: At the time of ICU admission
Severity of illness measured by MODS score
MODS
Measured: At the time of ICU admission
Change in severity of illness measured by APACHE score
APACHE
Measured: 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
Measured: 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
Measured: From the time of ICU admission, assessed daily until death or discharge from ICU, up to 12 months
Hospital disposition
Survival, death
Measured: Determined at the time of discharge from the hospital, through study completion, an average of 1 year
Secondary outcomes (2)
Neurocognitive dysfunction
Cambridge Brain Sciences (CBS) web-based neurocognitive battery
Measured: 1, 6, and 12 months after ICU discharge
Physiological outcomes
Ultrasound-identified volume responsiveness
Measured: 0, 24, 48, and 72 hours after ICU admission
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2022
- Study start26 Apr 2024
- Primary completion31 Dec 2034 (estimated)
- Study completion31 Dec 2034 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for SepsisStudies of the same condition, open and under way.
- More trials run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,000 participants (estimated)
- Target duration
- 24 Months
Sponsor and investigators
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- Sponsor type
- University, hospital or other
- Collaborators
- London Health Sciences Centre, Western University, Canada, Western University
- Responsible party
- Principal investigator, Aleks Leligdowicz, London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- Investigators
- Aleks Leligdowicz, MD PhD, Principal investigator, Western University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05591924
- Sponsor's protocol ID
- 12145
- Acronym
- ESTABLISH
- Status last verified
- Oct 2025
- First submitted
- 5 Oct 2022
- Last updated
- 6 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Biological specimen stored for future research may be eligible for collaborative future studies. Collaborators will be required to complete a study plan and be approved by the Lawson ethics board and/or the Western University HSREB.
Publications
Leligdowicz A, Matthay MA. Heterogeneity in sepsis: new biological evidence with clinical applications. Crit Care. 2019 Mar 9;23(1):80. doi: 10.1186/s13054-019-2372-2.
PubMed 30850013Maslove DM, Tang B, Shankar-Hari M, Lawler PR, Angus DC, Baillie JK, Baron RM, Bauer M, Buchman TG, Calfee CS, Dos Santos CC, Giamarellos-Bourboulis EJ, Gordon AC, Kellum JA, Knight JC, Leligdowicz A, McAuley DF, McLean AS, Menon DK, Meyer NJ, Moldawer LL, Reddy K, Reilly JP, Russell JA, Sevransky JE, Seymour CW, Shapiro NI, Singer M, Summers C, Sweeney TE, Thompson BT, van der Poll T, Venkatesh B, Walley KR, Walsh TS, Ware LB, Wong HR, Zador ZE, Marshall JC. Redefining critical illness. Nat Med. 2022 Jun;28(6):1141-1148. doi: 10.1038/s41591-022-01843-x. Epub 2022 Jun 17.
PubMed 35715504Leligdowicz A, Kamm J, Kalantar K, Jauregui A, Vessel K, Caldera S, Serpa PH, Abbott J, Fang X, Tian X, Prakash A, Kangelaris KN, Liu KD, Calfee CS, Langelier C, Matthay MA. Functional Transcriptomic Studies of Immune Responses and Endotoxin Tolerance in Early Human Sepsis. Shock. 2022 Jun 1;57(6):180-190. doi: 10.1097/SHK.0000000000001915. Epub 2022 Jan 20.
PubMed 35066510Leligdowicz A, Conroy AL, Hawkes M, Richard-Greenblatt M, Zhong K, Opoka RO, Namasopo S, Bell D, Liles WC, da Costa BR, Juni P, Kain KC. Risk-stratification of febrile African children at risk of sepsis using sTREM-1 as basis for a rapid triage test. Nat Commun. 2021 Nov 25;12(1):6832. doi: 10.1038/s41467-021-27215-6.
PubMed 34824252Leligdowicz A, Conroy AL, Hawkes M, Zhong K, Lebovic G, Matthay MA, Kain KC. Validation of two multiplex platforms to quantify circulating markers of inflammation and endothelial injury in severe infection. PLoS One. 2017 Apr 18;12(4):e0175130. doi: 10.1371/journal.pone.0175130. eCollection 2017.
PubMed 28419100Leligdowicz A, Chun LF, Jauregui A, Vessel K, Liu KD, Calfee CS, Matthay MA. Human pulmonary endothelial cell permeability after exposure to LPS-stimulated leukocyte supernatants derived from patients with early sepsis. Am J Physiol Lung Cell Mol Physiol. 2018 Nov 1;315(5):L638-L644. doi: 10.1152/ajplung.00286.2018. Epub 2018 Jul 19.
PubMed 30024307Marshall JC, Leligdowicz A. Gaps and opportunities in sepsis translational research. EBioMedicine. 2022 Dec;86:104387. doi: 10.1016/j.ebiom.2022.104387. Epub 2022 Dec 2.
PubMed 36470831Shah FA, Meyer NJ, Angus DC, Awdish R, Azoulay E, Calfee CS, Clermont G, Gordon AC, Kwizera A, Leligdowicz A, Marshall JC, Mikacenic C, Sinha P, Venkatesh B, Wong HR, Zampieri FG, Yende S. A Research Agenda for Precision Medicine in Sepsis and Acute Respiratory Distress Syndrome: An Official American Thoracic Society Research Statement. Am J Respir Crit Care Med. 2021 Oct 15;204(8):891-901. doi: 10.1164/rccm.202108-1908ST.
PubMed 34652268
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Observational Study of Biology of Critical Illness
- ClinicalTrials.gov ID
- NCT05591924
- Acronym / sponsor ID
- ESTABLISH / 12145
- Conditions
- Sepsis, ARDS, Critical Illness, Neurocognitive Dysfunction, Shock, Septic, Ventilator Associated Pneumonia
- Keywords
- Critical Care, Sepsis, ARDS, Inflammation, Immune responses, Neurocognition, Critical illness, Translational Biology
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 1,000 participants (estimated)
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sUniversity, hospital or other
- Collaborators
- London Health Sciences Centre, Western University, Canada, Western University
- Study start
- 26 Apr 2024 (actual)
- Primary completion
- 31 Dec 2034 (estimated)
- Study completion
- 31 Dec 2034 (estimated)
- First posted
- 24 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Background:
Critical illness syndromes, such as sepsis and ARDS, are associated with tremendous heterogeneity in patient predisposing risk factors, mechanisms of acute insult contributing to infection, presenting symptoms, response to therapies, as well as short and long-term outcomes. Since the first standardization of sepsis and ARDS definitions >30 years ago, significant insight into biological mechanisms contributing to critical illness syndromes have been made. However, there are many important unanswered questions that prevent accurate diagnosis, treatment, and prognosis of patients who present to the ICU with early symptoms consistent with critical illness.
Of the many gaps about the biology of sepsis and ARDS that remain unanswered, the following are particularly important: (1) what constitutes immune system dysregulation; (2) how the immune system response depends on interaction with the infecting pathogens; (3) what biologic traits distinguish other diagnoses that mimic these syndromes; (4) what are the mechanisms of genetic polymorphisms in patient outcomes. To address these questions and to improve our understanding of these complex and heterogenous syndromes, a multifaceted and collaborative approach is needed. This study will investigate the biology of early sepsis in critically ill patients by developing a longitudinal prospective observational cohort called Early Severe illness TrAnslational BioLogy InformaticS in Humans (ESTABLISH).
Specific objectives:
Objective 1: To study biologic mechanisms of immune system regulation during early critical illness. The main questions that will be addressed include: (1) how immune function at the time of admission and over the course of the ICU stay is related to clinical complications; (2) how anatomic compartmentalization of immune responses is associated with clinical complications; (3) how immune responses in different anatomic locations contribute to endothelial cell injury; (4) how macrophages contribute to distal organ injury and long-term clinical complications.
Objective 2: To characterize the host-pathogen interaction during early critical illness. The main question that will be addressed include: (1) how the microbial composition at the time of ICU admission affects the immune response; (2) how the change in host-pathogen interactions over time influence clinical complications.
Objective 3: To identify biologic traits that distinguish patients with early sepsis and ARDS from other critically ill patients. The main questions that will be addressed include: (1) are biological trains unique to sepsis and/or ARDS, or are they shared by other clinical diagnoses that mimic these syndromes?; (2) can accurately prognosticate clinically important short and long-term patient outcomes?; (3) are biologic traits associated with differential responses to therapies?
Objective 4: To study the molecular mechanisms of genetic polymorphisms associated with critical illness using induced pluripotent stem cells (iPSCs) derived from polymorphonuclear cells (PBMCs) from critically ill patients. The main questions that will be addressed include: (1) how do autologous iPSC-derived cell lineages interact with autologous plasma?; (2) how do iPSC-derived cell lineages respond to treatment with drugs related to genetic polymorphisms function?; (3) how do iPSC-derived lineages respond to treatment with drugs commonly used in the ICU?
Methods:
The ESTABLISH cohort will enroll patients within 48 hours of ICU admission who presented to the emergency department within 72 hours of ICU admission. Patients will be enrolled with deferred consent to enable the earliest possible collection of biological specimen. The biological specimen will include anticoagulated blood, a PAX gene tube, and a bronchioalveolar lavage fluid (BALF) sample (in mechanically ventilated patients, when bronchoscopy is clinically indicated) collected at the time of ICU admission (Day 0), and on 4 subsequent timepoints during the ICU admission (Days 1,3,7,14,21).
Data generated during ESTABLISH will be analyzed in batches on an ongoing, regular basis and will be objective-specific. Batch sample preparation and data analysis will minimize biological assay and methodological heterogeneity. Objective 1 and 2 data will be analyzed after enrollment of the first 50 patients, and every 50 patients after this. Objective 3 data will be analyzed after enrollment of the first 200 patients and every 200 patients after this.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 24 Months
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ESTABLISH | – | Procedure: Phelebotomy, Procedure: Broncheoalveolar Lavage, Procedure: Tracheal Aspirate, Procedure: Rectal SwabAdults 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. |
| Healthy Controls | – | Procedure: PhelebotomyAdults 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Critically ill adults with early critical illness
Key inclusion criteria (8 listed)
- 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:
Key exclusion criteria (4 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PhelebotomyCollection of 10mL of heparin anticoagulated blood, 10mL of EDTA anticoagulated blood, and 3mL of blood in a PAX gene tube | Procedure or surgery | ESTABLISH, Healthy Controls |
| Broncheoalveolar LavageBronchioalveolar 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. | Procedure or surgery | ESTABLISH |
| Tracheal AspirateTracheal 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. | Procedure or surgery | ESTABLISH |
| Rectal SwabA Rectal will be obtained at the time of ICU admission and on all study days during the ICU admission | Procedure or surgery | ESTABLISH |
Primary outcome
Risk of developing nosocomial infections during ICU admission
Time frame: Assessed daily until discharge from ICU, through study completion, an average of 1 year
Development of any of the following: Ventilator Associated Pneumonia, Central Line Infections, Clostridium difficile-Associated Diarrhea, Blood stream infections
Severity of illness measured by APACHE score
Time frame: At the time of ICU admission
APACHE
Severity of illness measured by SOFA score
Time frame: At the time of ICU admission
SOFA
Severity of illness measured by MODS score
Time frame: At the time of ICU admission
MODS
Change in severity of illness measured by APACHE score
Time frame: From the time of ICU admission, assessed daily until death or discharge from ICU, up to 12 months
APACHE
Change in severity of illness measured by SOFA score
Time frame: From the time of ICU admission, assessed daily until death or discharge from ICU, up to 12 months
SOFA
Change in severity of illness measured by MODS score
Time frame: From the time of ICU admission, assessed daily until death or discharge from ICU, up to 12 months
MODS
Hospital disposition
Time frame: Determined at the time of discharge from the hospital, through study completion, an average of 1 year
Survival, death
2 secondary outcomes
Neurocognitive dysfunction
Time frame: 1, 6, and 12 months after ICU discharge
Physiological outcomes
Time frame: 0, 24, 48, and 72 hours after ICU admission
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2025.
- Background: PubMed 30850013Leligdowicz A, Matthay MA. Heterogeneity in sepsis: new biological evidence with clinical applications. Crit Care. 2019 Mar 9;23(1):80. doi: 10.1186/s13054-019-2372-2.
- Background: PubMed 35715504Maslove DM, Tang B, Shankar-Hari M, Lawler PR, Angus DC, Baillie JK, Baron RM, Bauer M, Buchman TG, Calfee CS, Dos Santos CC, Giamarellos-Bourboulis EJ, Gordon AC, Kellum JA, Knight JC, Leligdowicz A, McAuley DF, McLean AS, Menon DK, Meyer NJ, Moldawer LL, Reddy K, Reilly JP, Russell JA, Sevransky JE, Seymour CW, Shapiro NI, Singer M, Summers C, Sweeney TE, Thompson BT, van der Poll T, Venkatesh B, Walley KR, Walsh TS, Ware LB, Wong HR, Zador ZE, Marshall JC. Redefining critical illness. Nat Med. 2022 Jun;28(6):1141-1148. doi: 10.1038/s41591-022-01843-x. Epub 2022 Jun 17.
- Background: PubMed 35066510Leligdowicz A, Kamm J, Kalantar K, Jauregui A, Vessel K, Caldera S, Serpa PH, Abbott J, Fang X, Tian X, Prakash A, Kangelaris KN, Liu KD, Calfee CS, Langelier C, Matthay MA. Functional Transcriptomic Studies of Immune Responses and Endotoxin Tolerance in Early Human Sepsis. Shock. 2022 Jun 1;57(6):180-190. doi: 10.1097/SHK.0000000000001915. Epub 2022 Jan 20.
- Background: PubMed 34824252Leligdowicz A, Conroy AL, Hawkes M, Richard-Greenblatt M, Zhong K, Opoka RO, Namasopo S, Bell D, Liles WC, da Costa BR, Juni P, Kain KC. Risk-stratification of febrile African children at risk of sepsis using sTREM-1 as basis for a rapid triage test. Nat Commun. 2021 Nov 25;12(1):6832. doi: 10.1038/s41467-021-27215-6.
- Background: PubMed 28419100Leligdowicz A, Conroy AL, Hawkes M, Zhong K, Lebovic G, Matthay MA, Kain KC. Validation of two multiplex platforms to quantify circulating markers of inflammation and endothelial injury in severe infection. PLoS One. 2017 Apr 18;12(4):e0175130. doi: 10.1371/journal.pone.0175130. eCollection 2017.
- Background: PubMed 30024307Leligdowicz A, Chun LF, Jauregui A, Vessel K, Liu KD, Calfee CS, Matthay MA. Human pulmonary endothelial cell permeability after exposure to LPS-stimulated leukocyte supernatants derived from patients with early sepsis. Am J Physiol Lung Cell Mol Physiol. 2018 Nov 1;315(5):L638-L644. doi: 10.1152/ajplung.00286.2018. Epub 2018 Jul 19.
- Background: PubMed 36470831Marshall JC, Leligdowicz A. Gaps and opportunities in sepsis translational research. EBioMedicine. 2022 Dec;86:104387. doi: 10.1016/j.ebiom.2022.104387. Epub 2022 Dec 2.
- Background: PubMed 34652268Shah FA, Meyer NJ, Angus DC, Awdish R, Azoulay E, Calfee CS, Clermont G, Gordon AC, Kwizera A, Leligdowicz A, Marshall JC, Mikacenic C, Sinha P, Venkatesh B, Wong HR, Zampieri FG, Yende S. A Research Agenda for Precision Medicine in Sepsis and Acute Respiratory Distress Syndrome: An Official American Thoracic Society Research Statement. Am J Respir Crit Care Med. 2021 Oct 15;204(8):891-901. doi: 10.1164/rccm.202108-1908ST.
- Individual participant dataSharing planned: Yes. Biological specimen stored for future research may be eligible for collaborative future studies. Collaborators will be required to complete a study plan and be approved by the Lawson ethics board and/or the Western University HSREB.
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Streptococcus Agalactiae Infection, Neonatal Sepsis
Active, not recruiting
CT for Personalized Mechanical Ventilation
Ventilator-Induced Lung Injury, Sepsis Syndrome
RecruitingPhase 4
A Study to Compare the Efficacy and Safety of Extended and Intermittent Infusion of Beta-lactams in Critically Ill Paediatric Patients
Infection, Sepsis
Not yet recruiting
Double Plasma Separation and Adsorption in Acute-on-Chronic Liver Failure (DPMAS-ACLF Trial)
Acute-on-Chronic Liver Failure (ACLF)
Active, not recruitingPhase 4
Thymosin Alpha 1 and IgM Levels in Sepsis
Sepsis, Septic Shock
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Aleks Leligdowicz, MD PhD principal investigator
Western University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Sepsis and ARDS, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Aleks Leligdowicz, MD PhD (519-661-2111 ext. 87241, aleligdo@uwo.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Risk of developing nosocomial infections during ICU admission (time frame: Assessed daily until discharge from ICU, through study completion, an average of 1 year). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05591924, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2025.