Precision Medicine for Post-Intensive Care Syndrome (PreMed4PICS)

NCT ID: NCT05518786

Last Updated: 2023-10-05

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 200 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-05-01
• Study Completion Date: 2025-05-31

Brief 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.

Detailed 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.

Conditions

Postintensive Care Syndrome

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

HUCA

Patients recruited at the University Central Hospital of Oviedo

Exposure of interest: critical illness

Intervention Type: OTHER

Patients admitted to an intensive care unit (ICU) will be followed-up to evaluate post-ICU long-term sequelae

Taulí

Patients recruited at Parc Taulí Foundation/Hospital (Sabadell)

Exposure of interest: critical illness

Intervention Type: OTHER

Patients admitted to an intensive care unit (ICU) will be followed-up to evaluate post-ICU long-term sequelae

Paz

Patients recruited at University Hospital of La Paz (Madrid)

Exposure of interest: critical illness

Intervention Type: OTHER

Patients admitted to an intensive care unit (ICU) will be followed-up to evaluate post-ICU long-term sequelae

Interventions

Exposure of interest: critical illness

Patients admitted to an intensive care unit (ICU) will be followed-up to evaluate post-ICU long-term sequelae

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Patients admitted to ICU

Exclusion Criteria

• Neurocritical patients
• Previous neurocognitive or muscular impairments
• Immunosuppression
• Known neoplasia
• Terminal illness

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fundación para la Investigación Biosanitaria del Principado de Asturias

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hospital Universitario Central de Asturias (HUCA)

Oviedo, Principality of Asturias, Spain

Site Status: RECRUITING

Countries

Spain

Facility Contacts

Laura Amado-Rodríguez, MD, PhD

Role: primary

lar@crit-lab.org

+34 985652433

Other Identifiers

CritLab_6

Identifier Type: -

Identifier Source: org_study_id