Clinical trial NCT05954260: Immune Dysfunction in Critical Illness: Utility of a Panel of Genes and Molecules Involved in the Immunological Synapse
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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Critical Illness
Keywords: Critical Illness
Lead sponsor: University of Valladolid
Sponsor class: OTHER
Collaborators: name: Hospital del Rio Hortega
name: Sanidad de Castilla y León
name: Instituto de Investigación Biomédica de Salamanca
name: Fundación Española del Enfermo Crítico (FEEC)
name: Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC)
First posted: 2023-07-20
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with any critical illness present in the ICU of the participating hospital.

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of patients with a functional immunosuppression signature
timeFrame: 5 days
measure: Mortality (28-day)
timeFrame: 28 days
measure: Hospital-Acquired Infection (28-day)
timeFrame: 28 days
measure: Organ Failure Resolution (28-day)
timeFrame: 28 days
Secondary outcomes:
measure: Mortality (90-day)
timeFrame: 90 days
measure: Hospital-Acquired Infection (90-day)
timeFrame: 90 days
measure: Duration of hospitalization in the ICU
timeFrame: 90 days
measure: Proportion of patients requiring organ support
timeFrame: 90 days
measure: Proportion of patients with early cardiac dysfunction
timeFrame: 5 days
measure: Proportion of patients with Herpesviridae reactivation
timeFrame: 90 days
measure: Proportion of patients with ICU-related complications
timeFrame: 90 days
measure: Proportion of patients with post-intensive care syndrome
timeFrame: 90 days
Other outcomes:
measure: Sex-related differences in the proportion of patients with a functional immunosuppression signature
timeFrame: 5 days
measure: Age-related differences in the proportion of patients with a functional immunosuppression signature
timeFrame: 5 days
measure: Nutritional status-related differences in the proportion of patients with a functional immunosuppression signature
timeFrame: 5 days
measure: Frailty status-related differences in the proportion of patients with a functional immunosuppression signature
timeFrame: 5 days
measure: Comorbid status-related differences in the proportion of patients with a functional immunosuppression signature
timeFrame: 5 days
measure: Diagnosis-related differences in the proportion of patients with a functional immunosuppression signature
timeFrame: 5 days
Locations:
city: Valladolid
country: Spain
facility: Hospital Universitario Río Hortega
Study officials:
affiliation: Hospital Universitario Río Hortega, Universidad de Valladolid
name: David Pérez-Torres, MD
role: PRINCIPAL_INVESTIGATOR
References: