Shock and Acute Conditions OutcOmes Platform

Sepsis Clinical Trial

— ShockCO-OP  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06376318
• Other study ID #: 19-138
• Status: Active, not recruiting
• Start date: January 1, 2024
• Est. completion date: January 1, 2026

Study information

• Verified date: April 2024
• Source: Saint-Louis Hospital, Paris, France
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1000
• Est. completion date: January 1, 2026
• Est. primary completion date: July 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cardiogenic Shock
• Circulatory Shock
• Major Trauma
• Sepsis
• Shock
• Shock, Cardiogenic
• Shock, Surgical

Intervention

Drug:
• Inotrope
Vasopressors: Norepinephrine, vasopressin Inotropes: Epinephrine, Dobutamine, Milrinone

Device:
• Mechanical circulatory support
Intra-aortic balloon pump Extracorporeal membrane oxygenation (ECMO)

Drug:
• anti-bodies
Anti-Dipeptidyl peptidase 3 (DPP3), Anti-Bioactive adrenomedullin (bio-ADM)

Locations

Country	Name	City	State
Canada	St Michael's Hospital	Toronto	Ontario

Sponsors (9)

Lead Sponsor	Collaborator
Saint-Louis Hospital, Paris, France	Mayo Clinic, McGill University, University of Helsinki, University of Leipzig, University of Nancy, University of Ottawa, University of Paris 5 - Rene Descartes, University of Toronto

Country where clinical trial is conducted

Canada, 

References & Publications (4)

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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mortality rate		28 days
Secondary	Mortality rate		1 year
Secondary	Renal replacement therapy use rate		28 days
Secondary	Mechanical circulatory support use rate		28 days
Secondary	Vasopressors and inotropes-free days		28 days