Shock and Acute Conditions OutcOmes Platform (ShockCO-OP)

Beyond the Syndromic Approach in Critical Care: Identifying Biomarker-driven Subphenotypes of Circulatory Shock

In-hospital mortality of patients admitted in the intensive care unit (ICU) for circulatory shock remains high (between 20 and 40%).

Currently, there are no markers that allow us to classify patients with circulatory shock at higher risk of early and late bad outcomes, or who may better respond to a specific intervention.

To understand the contribution of biological heterogeneity to circulatory shock independently from its etiology, the ShockCO-OP Research Program aims to use clustering approaches to re-analyze existing clinical and molecular data from several large European and North American prospective cohorts and clinical trials.

This will enable an improvement in risk prediction and a better patient selection in future clinical trials to assess a personalized therapy (i.e., prospective enrollment based on a biological/molecular signature).

Study Overview

• Status: Active, not recruiting
• Conditions: Sepsis; Cardiogenic Shock; Major Trauma; Circulatory Shock; Surgical Shock
• Intervention / Treatment: Drug: Inotrope; Device: Mechanical circulatory support; Drug: anti-bodies

Detailed Description

Traditionally, circulatory shock subgroups are defined according to hemodynamic profile (e.g., hypovolemic, distributive, cardiogenic) and etiology (e.g., trauma, infection, myocardial infarction among others) and are incorrectly considered as homogeneous clinical syndromes. Emerging translational evidence highlights the existing molecular heterogeneity in the circulatory shock syndrome. Such findings raise a major issue in assessing neutral clinical trial results in circulatory shock as a given intervention effect (e.g., fluid management, vasopressors/inotropes, mechanical circulatory support) may preferentially impact different subgroups (i.e., heterogeneity of treatment effect).

Accordingly, identifying distinct biological subphenotypes with different mechanistic signatures may provide new insights regarding the pathophysiology of circulatory shock. This may allow predictive enrichment (i.e., identifying those patients most likely to benefit from a particular therapy) and biomarker-driven or phenotype-driven patient selection in future clinical trials to assess a personalized therapy (i.e., prospective enrollment based on a biological signature).

The ShockCO-OP Research Program aims to use unsupervised model-based clustering (i.e., regardless of outcome) to reanalyze existing clinical and biological data in several European and North American prospective cohorts and clinical trials to identify distinct biomarker-driven subphenotypes in circulatory shock syndromes, their underlying molecular signatures (proteomics, transcriptomics), their association with outcome and their response to different interventions.

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5B 1W8
      • St Michael's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with circulatory shock on admission independently from its etiology

Description

Inclusion Criteria:

1. Patients with circulatory shock on admission (i.e., the reported main cause of admission is septic shock, cardiogenic shock or hypovolemic/hemorrhagic shock).
2. Patients who required vasopressors infusion and presented signs of tissue hypoperfusion (e.g., altered mental state (Glasgow coma scale≤ 14), oliguria (urine output of < 0.5 ml/kg/h for at least six hours) or a serum lactate level of ≥2 mmol/l) within the first 24 h after admission.

Exclusion Criteria:

1. Mechanical circulatory support on admission
2. Serious arrythmia (e.g., rapid atrial fibrillation or ventricular tachycardia/fibrillation) on admission
3. Deceased patients within the first 24 hours after admission.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mortality rate	28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Mortality rate	1 year
Renal replacement therapy use rate	28 days
Mechanical circulatory support use rate	28 days
Vasopressors and inotropes-free days	28 days

Collaborators and Investigators

• Sponsor: Saint-Louis Hospital, Paris, France
• Collaborators: Mayo Clinic; McGill University; University of Toronto; University of Leipzig; University of Ottawa; University of Helsinki; University of Paris 5 - Rene Descartes; University of Nancy
• Investigators: Principal Investigator: Claudia dos Santos, MD, PhD, Unity Health Toronto; Study Chair: Alexandre Mebazaa, MD, PhD, St Louis and Lariboisiere Hospitals

Publications and helpful links

General Publications

• Soussi S, Dos Santos C, Jentzer JC, Mebazaa A, Gayat E, Poss J, Schaubroeck H, Billia F, Marshall JC, Lawler PR. Distinct host-response signatures in circulatory shock: a narrative review. Intensive Care Med Exp. 2023 Aug 18;11(1):50. doi: 10.1186/s40635-023-00531-5.
• Sarma D, Jentzer JC, Soussi S. Cardiogenic shock: a major challenge for the clinical trialist. Curr Opin Crit Care. 2023 Aug 1;29(4):371-380. doi: 10.1097/MCC.0000000000001066. Epub 2023 Jun 19.
• Mebazaa A, Soussi S. Precision Medicine in Cardiogenic Shock: We Are Almost There! JACC Heart Fail. 2023 Oct;11(10):1316-1319. doi: 10.1016/j.jchf.2023.06.024. Epub 2023 Aug 16. No abstract available.
• Soussi S, Collins GS, Juni P, Mebazaa A, Gayat E, Le Manach Y. Evaluation of Biomarkers in Critical Care and Perioperative Medicine: A Clinician's Overview of Traditional Statistical Methods and Machine Learning Algorithms. Anesthesiology. 2021 Jan 1;134(1):15-25. doi: 10.1097/ALN.0000000000003600.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: April 1, 2024
• First Submitted That Met QC Criteria: April 16, 2024
• First Posted (Actual): April 19, 2024

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: machine learning; biomarkers; shock; heterogeneity of treatment effect
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Postoperative Complications; Myocardial Infarction; Infarction; Shock; Shock, Cardiogenic; Shock, Surgical; Physiological Effects of Drugs; Immunologic Factors; Antibodies
• Other Study ID Numbers: 19-138

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No