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NCT Number: NCT07510776

UP STUDY - Decipher Persistent Critical Illness Through in Deep Clinical Phenotyping.

Persistent Critical Illness (PCI) is a condition that affects some patients who remain in the Intensive Care Unit (ICU) for a long time, usually more than 10-14 days. It is estimated to occur in 5-20% of critically ill patients. A recent Portuguese study found that more than 14% of ICU patients stayed longer than 14 days. PCI is often associated with ongoing need for life support, such as mechanical ventilation or medications to maintain blood pressure. However, patients may also experience severe muscle weakness, repeated infections, or other complications, which makes this group very diverse.

One of the main risk factors for prolonged ICU stay is sepsis, a severe infection that affects the whole body. Other factors-such as prior health conditions, use of corticosteroids, sedation practices, early versus late mobilization, fluid and antibiotic management, and delirium treatment-may also influence the development and course of PCI.

This study aims to identify different clinical patterns ("clusters") among critically ill patients who remain in the ICU for more than 10 days. Patients will be followed until hospital discharge, and up to one year if data are available. Understanding these different patterns will help develop more personalized and effective care strategies for each patient profile.

The study is a multicenter retrospective cohort including adult patients (≥18 years) admitted to participating ICUs for more than 5 days between 2021 and 2023. Data collected will include demographic, clinical, and laboratory information, details of organ support (such as mechanical ventilation or vasopressors), medications, nutrition, and rehabilitation practices.

Statistical and machine learning methods will be used to identify groups of patients with similar clinical trajectories and to assess how these groups are related to outcomes such as survival, recovery of organ function, or long-term disability.

Expected results are the identification of distinct clinical clusters of PCI that combine clinical and laboratory data, and the development of tailored management strategies to improve recovery and outcomes for patients with PCI.

Recruiting

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Centro Hospitalar de São João / ULS São João, Lisbon, Lisbon District, Portugal

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Adult patients aged 18 years or older;
  • ICU length of stay equal to or greater than 5 days.

Exclusion criteria

  • Patients with an ICU stay < 5 days;
  • Patients discharged from the ICU early due to lack of ward availability, rather than clinical recovery;
  • Patients who do not survive the early phase of critical illness (i.e., early ICU deaths).

Treatment and study plan

Primary outcomes

  1. Need for one or more continuous organ support treatment at Day 10

    Time frame: The first 10 days in the ICU

    Data from patients who remain in the ICU for more than 10 days requiring ongoing organ support, such as invasive mechanical ventilation, renal replacement therapy or vasopressors, will be used to identify those who develop Persistent Critical Illness and to enable subsequent cluster analysis of their clinical trajectories.

Secondary outcomes

  1. All cause mortality stratified by Persistent Critical Illness (PCI) clusters

    Time frame: From cluster identification (Day 10) until hospital discharge or up to 1-year follow-up if available.

    Clinical outcomes will be assessed and reported according to clusters of Persistent Critical Illness (PCI) identified using unsupervised machine learning analysis at Day 10 of ICU stay. Outcome includes:

    • All-cause mortality, reported as the proportion of participants who die during hospitalization and up to 1 year after cluster identification.
  2. Organ dysfunction stratified by Persistent Critical Illness

    Time frame: From cluster identification (Day 10) until hospital discharge or up to 1-year follow-up if available.

    Clinical outcomes will be assessed and reported according to clusters of Persistent Critical Illness (PCI) identified using unsupervised machine learning analysis at Day 10 of ICU stay. Outcome includes:

    • Organ dysfunction, assessed using the Sequential Organ Failure Assessment (SOFA) score, reported as mean (± SD) or median (IQR) values after cluster identification.

Other outcomes

  1. ICU mortality

    Time frame: Through ICU stay (up to 1 year).

    Death occurring at any time during the ICU stay.

  2. Hospital mortality

    Time frame: Through hospital stay (up to 2 years).

    Death occurring at any time during the hospital admission.

  3. ICU length of stay

    Time frame: Through ICU stay (up to 1 year).

    Total number of calendar days from ICU admission to ICU discharge.

  4. Incidence of ICU-acquired infections

    Time frame: Through ICU stay (up to 1 year).

    Number of clinically or microbiologically documented infections acquired ≥48 hours after ICU admission.

  5. Hemoglobin trajectory

    Time frame: Through ICU stay (up to 1 year).

    Longitudinal assessment of hemoglobin levels using repeated measurements obtained during the intensive care unit (ICU) stay.

  6. C-reactive protein (CRP) trajectory

    Time frame: Through ICU stay (up to 1 year).

    Longitudinal assessment of C-reactive protein levels using repeated measurements obtained during the intensive care unit stay.

  7. Creatinine trajectory

    Time frame: Through ICU stay (up to 1 year).

    Longitudinal assessment of creatinine levels using repeated measurements obtained during the intensive care unit stay.

  8. Albumin trajectory

    Time frame: Through ICU stay (up to 1 year).

    Longitudinal assessment of albumin levels using repeated measurements obtained during the intensive care unit stay.

  9. Lactate trajectory

    Time frame: Through ICU stay (up to 1 year).

    Longitudinal assessment of lactate levels using repeated measurements obtained during the intensive care unit stay.

Study contacts

Contact information is provided by the study sponsor or research team.

Mariana Santos, PhD

CONTACT

[email protected]

351 21 798 5100

Susana Fernandes, MD PhD.

CONTACT

[email protected]

351 21 798 5100

Sponsors and collaborators

Lead sponsor

Lisbon Academic Medical Center - Centro Académico de Medicina de Lisboa

Network

Collaborators

  • Centro Hospitalar De São João, E.P.E.
  • Centro Hospitalar Lisboa Ocidental
  • Centro Hospitalar de Vila Nova de Gaia/Espinho
  • Hospital Prof. Doutor Fernando Fonseca
  • Hospital Vila Franca de Xira
  • Unidade Local de Saúde Almada-Seixal

Registry information

Acronym: UPSt_UCI

Important dates

Study start
2025
Primary completion
2026
Study completion
2027
First posted
Apr 3, 2026
Registry last updated
Apr 13, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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