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

Recruiting

• Conditions: Critical Illness

• Registration Number: NCT05954260
• Lead Sponsor: David Pérez Torres

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-07-12
• Study First Submitted QC: 2023-07-12
• Study First Posted: 2023-07-20
• Status Verified: 2023-08
• Study Start: 2023-08-20
• Last Update Submitted: 2023-08-20
• Last Update Posted: 2023-08-23
• Primary Completion: 2024-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Hospital-Acquired Infection (90-day)	90 days	Number of patients developing hospital-acquired infections in the groups with and without an early functional immunosuppression signature.
Mortality (90-day)	90 days	Number of non-surviving patients in the groups with and without an early functional immunosuppression signature.
Proportion of patients with early cardiac dysfunction	5 days	Number of patients who develop early cardiac dysfunction, as assessed by echocardiography, in the groups with and without an early functional immunosuppression signature.
Duration of hospitalization in the ICU	90 days	Length of stay in the ICU in the groups with and without an early functional immunosuppression signature.
Proportion of patients requiring organ support	90 days	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.
Proportion of patients with Herpesviridae reactivation	90 days	Number of patients who develop Herpesviridae reactivation during ICU admission, in the groups with and without an early functional immunosuppression signature.
Proportion of patients with ICU-related complications	90 days	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.
Proportion of patients with post-intensive care syndrome	90 days	Number of patients who develop post-intensive care syndrome, in the groups with and without an early functional immunosuppression signature.

Trial Locations

Locations (1)

Hospital Universitario Río Hortega; 🇪🇸 Valladolid, Spain