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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05518786
Other study ID # CritLab_6
Secondary ID
Status Recruiting
Phase
First received
Last updated
Start date May 1, 2020
Est. completion date May 31, 2025

Study information

Verified date October 2023
Source Fundación para la Investigación Biosanitaria del Principado de Asturias
Contact n/a
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

Critically ill patients show an acute phase characterized by systemic spread of the inflammatory response, irrespectively of the cause of intensive care unit (ICU) admission, and late sequelae, including ICU acquired muscle weakness (ICUAW) and neurocognitive impairment. Mechanisms driving these late sequelae are unknown and there are no effective therapies to date. PreMed4PICS hypothesis is that skeletal muscle pathogenetic phenotypes and long-term sequelae in survivors to critical illness can be predicted at ICU admission in peripheral blood samples by transcriptomic profiling of the acute systemic response. Our main objective is to identify pathogenesis-dependent predictive signatures of muscle injury and clinical outcomes such as ICUAW or cognitive impairment. A multicentric prospective observational study will be conducted including adult patients admitted to the ICU and followed up until 12 months after ICU discharge. This will allow for clinical subphenotyping, sample acquisition and histopathological studies. To identify subphenotype-specific molecular pathways involved in skeletal muscle recovery, single-nuclei RNAseq will be performed. Massive sequencing of whole blood RNA and circulating microRNA at ICU admission will be performed to identify transcriptomic signatures that result in quantitative scores predictive of the outcomes of interest. All the findings will be confirmed in two validation cohorts. Collectively, this project aims to characterize the molecular mechanisms leading to ICUAW development and recovery, identifying therapeutic targets. The potential of a quantitative approach to the acute inflammatory response to predict long-term sequelae in survivors of critical illness will be validated.


Description:

The main objective of this project is to demonstrate that transcriptomic profiling of the acute systemic inflammatory response in patients admitted to the ICU predicts the main molecular pathways activated in the skeletal muscle at the onset of critical illness and during recovery, and the long term post-ICU sequelae. To achieve this objective the following specific aims have been established and organized into four work packages (WP) with specific objectives: WP1: Clinical subphenotying and sampling in a large cohort of critically ill patients. WP1.1. To characterize clinical features of the acute response to critical illness in two independents cohorts. WP1.2. To evaluate long-term post-ICU sequelae after ICU discharge. WP1.3. To create a biobanked collection of samples from critically-ill patients. WP2: Pathogenetic subphenotyping of skeletal muscle injury and recovery in critically ill patients. WP2.1. To perform sn-RNAseq in muscle samples obtained at ICU admission and during the recovery phase from patients with and without persistent postICU muscle weakness. WP2.2. To identify local pathogenetic subphenotypes according to the mechanisms involved in ICUAW development and recovery. WP3: Transcriptomic profiling of peripheral whole blood during the acute response to critical illness. WP3.1. To massively sequence gene expression and c-miRNA in peripheral blood obtained at ICU admission (discovery cohort). WP3.2. To identify transcriptomic signatures in peripheral blood predictive of pathogenetic muscular phenotypes and long-term post-ICU sequelae. WP3.3. To characterize the acute inflammatory profiles in response to critical illness according to the transcriptomic signatures.


Recruitment information / eligibility

Status Recruiting
Enrollment 200
Est. completion date May 31, 2025
Est. primary completion date December 30, 2023
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Patients admitted to ICU Exclusion Criteria: - Neurocritical patients - Previous neurocognitive or muscular impairments - Immunosuppression - Known neoplasia - Terminal illness

Study Design


Related Conditions & MeSH terms


Intervention

Other:
Exposure of interest: critical illness
Patients admitted to an intensive care unit (ICU) will be followed-up to evaluate post-ICU long-term sequelae

Locations

Country Name City State
Spain Hospital Universitario Central de Asturias (HUCA) Oviedo Principado De Asturias

Sponsors (1)

Lead Sponsor Collaborator
Fundación para la Investigación Biosanitaria del Principado de Asturias

Country where clinical trial is conducted

Spain, 

Outcome

Type Measure Description Time frame Safety issue
Primary ICU-acquired weakness Presence or absence of muscle weakness after critical illness at 12 months after ICU discharge. 1 year
Primary Neurocognitive impairment Presence or absence of neurocognitive impairment in survivors of critical illness at 12 months after ICU discharge 1 year
Secondary All-cause mortality All-cause mortality 1 year
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