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

NCT05954260 | Unknown

• 3 other identifiers: EFIMEROFEEC 2022/001GRS 2618/A/22
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Critical Illness

Keywords

Critical Illness

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (8)

• Mortality (90-day)

  90 days

• Hospital-Acquired Infection (90-day)

  90 days

• Duration of hospitalization in the ICU

  90 days

• Proportion of patients requiring organ support

  90 days

• Proportion of patients with early cardiac dysfunction

  5 days

Other Outcomes (6)

• Sex-related differences in the proportion of patients with a functional immunosuppression signature

  5 days

• Age-related differences in the proportion of patients with a functional immunosuppression signature

  5 days

• Nutritional status-related differences in the proportion of patients with a functional immunosuppression signature

  5 days

Interventions

Blood sampling DIAGNOSTIC_TEST

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• David Pérez Torres: lead
• Hospital del Rio Hortega: collaborator
• Sanidad de Castilla y León: collaborator
• Instituto de Investigación Biomédica de Salamanca: collaborator
• Fundación Española del Enfermo Crítico (FEEC): collaborator
• Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC): collaborator

Study Sites (1)

Hospital Universitario Río Hortega

Valladolid, 47012, Spain

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

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.

MeSH Terms

Conditions

Critical Illness

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• David Pérez-Torres, MD

  Hospital Universitario Río Hortega, Universidad de Valladolid

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David Pérez-Torres, MD

CONTACT

983420400; inmunologia-criticos@saludcastillayleon.onmicrosoft.com

Luis Mariano Tamayo-Lomas, MD, PhD

CONTACT

983420400; inmunologia-criticos@saludcastillayleon.onmicrosoft.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 12, 2023
• First Posted: July 20, 2023
• Study Start: August 20, 2023
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2025
• Last Updated: August 23, 2023

Record last verified: 2023-08

Locations

ES (1)