Early Severe Illness TrAnslational BioLogy InformaticS in Humans
NCT ID: NCT05591924
Last Updated: 2025-10-06
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
1000 participants
OBSERVATIONAL
2024-04-26
2034-12-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
EVLWI Exhibits Pulmonary and Systemic Permeability in Sepsis Related ALI/ARDS
NCT01694147
Early Biological and Mechanical Profiling in Sepsis-Associated ARDS
NCT07281911
Large Observational Study to UNderstand the Global Impact of Severe Acute Respiratory FailurE
NCT02010073
French and EuRopean Outcome Registry in Intensive Care Unit
NCT01367093
Early Recognition and Dynamic Risk Warning System of Multiple Organ Dysfunction Syndrome Caused by Sepsis
NCT04904289
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
COHORT
PROSPECTIVE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
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.
Phelebotomy
Collection of 10mL of heparin anticoagulated blood, 10mL of EDTA anticoagulated blood, and 3mL of blood in a PAX gene tube
Broncheoalveolar Lavage
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 Aspirate
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 Swab
A Rectal will be obtained at the time of ICU admission and on all study days during the ICU admission
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.
Phelebotomy
Collection of 10mL of heparin anticoagulated blood, 10mL of EDTA anticoagulated blood, and 3mL of blood in a PAX gene tube
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Phelebotomy
Collection of 10mL of heparin anticoagulated blood, 10mL of EDTA anticoagulated blood, and 3mL of blood in a PAX gene tube
Broncheoalveolar Lavage
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 Aspirate
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 Swab
A Rectal will be obtained at the time of ICU admission and on all study days during the ICU admission
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* ≤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:
1. Altered mental status (GCS\<15)
2. Cardiovascular collapse (presence of any: Heart rate \>90, systolic blood pressure \<90, presence of vasopressors, lactate \>2.0)
3. Respiratory collapse (presence of any: respiratory rate \>20, PaCO₂ \<32 mm Hg, supplemental oxygen, invasive or non-invasive ventilation)
4. 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)
Exclusion Criteria
* \>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)
18 Years
ALL
Yes
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
London Health Sciences Centre
OTHER
Western University, Canada
OTHER
Western University
OTHER
London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Aleks Leligdowicz
Clinician Scientist
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Aleks Leligdowicz, MD PhD
Role: PRINCIPAL_INVESTIGATOR
Western University
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Aleks Leligdowicz
London, Ontario, Canada
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
References
Explore related publications, articles, or registry entries linked to this study.
Micic S, Illic V, Isvaneski M. Correlation of hormone and histologic parameters in infertile men with varicocele. Urol Int. 1983;38(3):187-90. doi: 10.1159/000280888.
Maslove 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.
Jung RT. Obesity as a disease. Br Med Bull. 1997;53(2):307-21. doi: 10.1093/oxfordjournals.bmb.a011615.
Yacubian EM, Rosemberg S, Marie SK, Valerio RM, Jorge CL, Cukiert A. Double pathology in Rasmussen's encephalitis: etiologic considerations. Epilepsia. 1996 May;37(5):495-500. doi: 10.1111/j.1528-1157.1996.tb00597.x.
Tandon SP, Mishra MM. Effect of sodium, manganese and zinc on the activity of nitrobacter agilis. Zentralbl Bakteriol Parasitenkd Infektionskr Hyg. 1969;123(4):399-402. No abstract available.
Yoshino M, Murakami K. The regulatory role of spermine and fatty acid in the interaction of AMP deaminase with phosphofructokinase. Biochim Biophys Acta. 1982 Dec 17;719(3):474-9. doi: 10.1016/0304-4165(82)90235-5.
Aono R. Improvement of organic solvent tolerance level of Escherichia coli by overexpression of stress-responsive genes. Extremophiles. 1998 Aug;2(3):239-48. doi: 10.1007/s007920050066.
Kaplan A, Matsue H, Shibaki A, Kawashima T, Kobayashi H, Ohkawara A. The effects of cyclosporin A and FK506 on proliferation and IL-8 production of cultured human keratinocytes. J Dermatol Sci. 1995 Sep;10(2):130-8. doi: 10.1016/0923-1811(95)00395-9.
Study Documents
Access uploaded study-related documents such as protocols, statistical analysis plans, or lay summaries.
Document Type: C3RP Laboratory Website
View DocumentOther Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
12145
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.