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

Critical Illness Clinical Trial

— EFIMERO  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05954260
• Other study ID #: EFIMERO
• Secondary ID: FEEC 2022/001GRS
• Status: Recruiting
• Start date: August 20, 2023
• Est. completion date: December 31, 2025

Study information

• Verified date: August 2023
• Source: University of Valladolid
• Contact: David Pérez-Torres, MD
• Phone: 983420400
• Email: inmunologia-criticos[@]saludcastillayleon.onmicrosoft.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Critical Illness

Intervention

Diagnostic Test:
• Blood sampling
We will collect blood samples from the patients included in the study on ICU days 1, 3 and 5. We will measure gene expression (mRNA) and plasma levels of various elements involved in the immunological synapse.

Locations

Country	Name	City	State
Spain	Hospital Universitario Río Hortega	Valladolid

Sponsors (6)

Lead Sponsor	Collaborator
David Pérez Torres	Fundación Española del Enfermo Crítico (FEEC), Hospital del Río Hortega, Instituto de Investigación Biomédica de Salamanca, Sanidad de Castilla y León, Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC)

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Primary	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
Primary	Mortality (28-day)	Number of non-surviving patients in the groups with and without an early functional immunosuppression signature.	28 days
Primary	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
Primary	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	Mortality (90-day)	Number of non-surviving patients in the groups with and without an early functional immunosuppression signature.	90 days
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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