Immune Dysfunction in Critical Illness: Utility of a Panel of Genes and Molecules Involved in the Immunological Synapse (EFIMERO)

Cuantificación de la Disfunción Inmunitaria Inducida Por la Enfermedad Crítica Mediante el Estudio de un Panel de Genes y Moléculas Implicadas en la Sinapsis Inmunológica y su Utilidad Pronóstica

Critical illnesses represent a significant physiological assault that triggers changes in the patient's immune system, resulting in an immunopotentiating response (systemic inflammatory response syndrome, SIRS) and an immunosuppressive response (compensatory anti-inflammatory response syndrome, CARS). The balance between SIRS and CARS is essential for the patient to return to a state of immune homeostasis and accelerate the healing process. However, when CARS is disproportionately intense, it leads to a state of immunoparalysis, which predisposes the patient to vulnerability to opportunistic infections, associated with a peak in late mortality. The majority of patients admitted to the ICU are considered immunocompetent. However, the investigators suspect that a significant proportion of them exhibit predominance of CARS and a state of functional immunosuppression. There is currently no diagnostic test to determine whether a patient is functionally immunocompetent at a specific point in time.

The goal of this observational study is to learn about the immune system dysfunction occurring in critical illness. The main questions it aims to answer are:

• What is the prevalence of immune system dysfunction in critical illness?
• Does immune system dysfunction affect multiple organ failure trajectory and mortality in critical illness?
• Is immune system dysfunction related to an increased risk of opportunistic hospital-acquired infections in critical illness?
• Is immune system dysfunction related to age, fragility, nutritional status or previous comorbidities in critical illness?

To answer these questions, the investigators will prospectively study a population of critically ill patients, defined by the presence of organ failure. The investigators will analyse a panel of genes and molecules involved in immunological synapse, using peripheral blood samples at different moments of the evolution of critical illness. Based on the analysis, the investigators will classify the patients' functional immune status and correlate it with the outcomes.

Study Overview

• Status: Recruiting
• Conditions: Critical Illness
• Intervention / Treatment: Diagnostic test: Blood sampling

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: David Pérez-Torres, MD; Phone Number: 83719 983420400; Email: inmunologia-criticos@saludcastillayleon.onmicrosoft.com
• Study Contact Backup: Name: Luis Mariano Tamayo-Lomas, MD, PhD; Phone Number: 83719 983420400; Email: inmunologia-criticos@saludcastillayleon.onmicrosoft.com

Study Locations

• Spain
  • Valladolid, Spain, 47012
    • Recruiting
    • Hospital Universitario Rio Hortega
    • Contact: David Pérez-Torres, MD; Phone Number: 83719 983420400; Email: inmunologia-criticos@saludcastillayleon.onmicrosoft.com

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

Patients with any critical illness present in the ICU of the participating hospital.

Description

Inclusion Criteria:

• Failure of one or more organs, assessed by a Sequential Organ Failure Assessment Score (SOFA) ≥4 within the first 24 hours of admission to the Intensive Care Unit (ICU). At least one of the physiological systems involved must be in the category of organ failure and, therefore, score ≥3.
• Informed consent to participate in the study.
• Age equal to or greater than 18 years.

Exclusion Criteria:

• Pharmacological immunosuppression within the 3 months prior to the current admission date, including treatment with corticosteroids, immunosuppressive drugs (conventional or biological), or chemotherapy.
• Immunodeficiency.
• Age under 18 years.
• Absence of consent to participate in the study.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with a functional immunosuppression signature	Number of patients with organ failure exhibiting an early transcriptomic signature denoting depression of the immunological synapse.	5 days
Mortality (28-day)	Number of non-surviving patients in the groups with and without an early functional immunosuppression signature.	28 days
Hospital-Acquired Infection (28-day)	Number of patients developing hospital-acquired infections in the groups with and without an early functional immunosuppression signature.	28 days
Organ Failure Resolution (28-day)	Number of patients with organ failure resolution in the groups with and without an early functional immunosuppression signature.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality (90-day)	Number of non-surviving patients in the groups with and without an early functional immunosuppression signature.	90 days
Hospital-Acquired Infection (90-day)	Number of patients developing hospital-acquired infections in the groups with and without an early functional immunosuppression signature.	90 days
Duration of hospitalization in the ICU	Length of stay in the ICU in the groups with and without an early functional immunosuppression signature.	90 days
Proportion of patients requiring organ support	Number of patients who require organ support (mechanical ventilation, vasopressors, renal replacement therapy, extracorporeal membrane oxygenation,...) in the groups with and without an early functional immunosuppression signature.	90 days
Proportion of patients with early cardiac dysfunction	Number of patients who develop early cardiac dysfunction, as assessed by echocardiography, in the groups with and without an early functional immunosuppression signature.	5 days
Proportion of patients with Herpesviridae reactivation	Number of patients who develop Herpesviridae reactivation during ICU admission, in the groups with and without an early functional immunosuppression signature.	90 days
Proportion of patients with ICU-related complications	Number of patients who develop ICU-related complications during ICU admission, including ICU-acquired weakness, delirium, thrombosis or bleeding, in the groups with and without an early functional immunosuppression signature.	90 days
Proportion of patients with post-intensive care syndrome	Number of patients who develop post-intensive care syndrome, in the groups with and without an early functional immunosuppression signature.	90 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sex-related differences in the proportion of patients with a functional immunosuppression signature	Number of patients with organ failure exhibiting an early transcriptomic signature denoting depression of the immunological synapse, grouped by sex category.	5 days
Age-related differences in the proportion of patients with a functional immunosuppression signature	Number of patients with organ failure exhibiting an early transcriptomic signature denoting depression of the immunological synapse, grouped by predefined age categories.	5 days
Nutritional status-related differences in the proportion of patients with a functional immunosuppression signature	Number of patients with organ failure exhibiting an early transcriptomic signature denoting depression of the immunological synapse, grouped by nutritional status on ICU admission.	5 days
Frailty status-related differences in the proportion of patients with a functional immunosuppression signature	Number of patients with organ failure exhibiting an early transcriptomic signature denoting depression of the immunological synapse, grouped by frailty status on ICU admission.	5 days
Comorbid status-related differences in the proportion of patients with a functional immunosuppression signature	Number of patients with organ failure exhibiting an early transcriptomic signature denoting depression of the immunological synapse, grouped by previous comorbidities.	5 days
Diagnosis-related differences in the proportion of patients with a functional immunosuppression signature	Number of patients with organ failure exhibiting an early transcriptomic signature denoting depression of the immunological synapse, grouped by diagnostic category on ICU admission.	5 days

Collaborators and Investigators

• Sponsor: David Pérez Torres
• Collaborators: Instituto de Investigación Biomédica de Salamanca; Hospital del Rio Hortega; Sanidad de Castilla y León; Fundación Española del Enfermo Crítico (FEEC); Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC)
• Investigators: Principal Investigator: David Pérez-Torres, MD, Hospital Universitario Río Hortega, Universidad de Valladolid

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2023
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: July 12, 2023
• First Submitted That Met QC Criteria: July 12, 2023
• First Posted (Actual): July 20, 2023

Study Record Updates

• Last Update Posted (Actual): August 23, 2023
• Last Update Submitted That Met QC Criteria: August 20, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Critical Illness
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness
• Other Study ID Numbers: EFIMERO; FEEC 2022/001 (Other Grant/Funding Number: SEMICYUC); GRS 2618/A/22 (Other Grant/Funding Number: Gerencia Regional de Salud de Castilla y León (SACYL))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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