Clinical trial NCT06376318: Shock and Acute Conditions OutcOmes Platform
Official title: Beyond the Syndromic Approach in Critical Care: Identifying Biomarker-driven Subphenotypes of Circulatory Shock
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Circulatory Shock
Sepsis
Cardiogenic Shock
Major Trauma
Surgical Shock
Keywords: shock
heterogeneity of treatment effect
biomarkers
machine learning
Lead sponsor: Saint-Louis Hospital, Paris, France
Sponsor class: OTHER
Collaborators: name: University of Helsinki
name: University of Ottawa
name: University of Leipzig
name: University of Nancy
name: McGill University
name: Mayo Clinic
name: University of Paris 5 - Rene Descartes
name: University of Toronto
First posted: 2024-04-19
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with circulatory shock on admission independently from its etiology

Brief summary: 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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Mortality rate
timeFrame: 28 days
Secondary outcomes:
measure: Mortality rate
timeFrame: 1 year
measure: Renal replacement therapy use rate
timeFrame: 28 days
measure: Mechanical circulatory support use rate
timeFrame: 28 days
measure: Vasopressors and inotropes-free days
timeFrame: 28 days
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: St Michael's Hospital
state: Ontario
Study officials:
affiliation: Unity Health Toronto
name: Claudia dos Santos, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: St Louis and Lariboisiere Hospitals
name: Alexandre Mebazaa, MD, PhD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.