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RecruitingNCT07510776UPSt_UCIUpdated Apr 13, 2026

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

An observational study in Critical Illness, Recovery Outcomes and Critical Care, Intensive Care, sponsored by Lisbon Academic Medical Center - Centro Académico de Medicina de Lisboa. Recruiting at 7 sites in Portugal. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-04-13.

Sponsored by Lisbon Academic Medical Center - Centro Académico de Medicina de Lisboa · Observational

Study type
Observational
Model
Cohort
Time perspective
Retrospective
Enrollment
7,000
Ages
18 Years and older
Sex
All
01

Study summary

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.

02

Conditions studied

  • Critical Illness
  • Recovery Outcomes
  • Critical Care, Intensive Care
  • Critical Care
  • Critical Care Medicine

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Keywords

  • Persistant Critical Illness
  • Critical care
  • Critical Illness
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No
Sampling method
Non-probability sample

Study population

This study will include adult patients (≥18 years old) who are consecutively admitted to participating intensive care units (ICUs) and remain in the ICU for 5 or more days. The focus will be on patients who survive the early phase of critical illness, allowing the formation of a relatively homogeneous cohort of early ICU survivors.

The population will comprise patients with a wide range of critical illnesses, including sepsis, respiratory failure, cardiovascular instability, and multi-organ dysfunction, who require ongoing organ support such as invasive mechanical ventilation or vasopressors. Patients with prolonged ICU stays exceeding 10 days who continue to require organ support will be further characterized as having Persistent Critical Illness.

Inclusion criteria

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

Exclusion criteria

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).
04

Study design

Observational model
Cohort
Time perspective
Retrospective
Enrollment
7,000 participants (estimated)
Patient registry
No

Groups and cohorts

  • Adult patients (≥18 years) admitted to participating ICUs for more than 5 days.

    Adult patients (≥18 years) admitted to participating intensive care units (ICUs) who remained in the ICU for more than 5 days.

05

What researchers measure

Primary outcomes

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

    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.

    Time frame: The first 10 days in the ICU

Secondary outcomes

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

    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.

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

  2. Organ dysfunction stratified by Persistent Critical Illness

    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.

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

Other outcomes

  1. ICU mortality

    Death occurring at any time during the ICU stay.

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

  2. Hospital mortality

    Death occurring at any time during the hospital admission.

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

  3. ICU length of stay

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

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

  4. Incidence of ICU-acquired infections

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

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

  5. Hemoglobin trajectory

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

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

  6. C-reactive protein (CRP) trajectory

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

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

  7. Creatinine trajectory

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

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

  8. Albumin trajectory

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

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

  9. Lactate trajectory

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

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

06

Study locations

6 of 7 sites recruiting
  • Centro Hospitalar de São João / ULS São João
    Lisbon, Lisbon District, Portugal
    • José Artur Paiva, MD PhD · Contact · japaiva@ulssjoao.min-saude.pt · 351 225 512 100
    • José Artur Paiva, MD PhD · Principal investigator
    • Cristiana Paulo, MD PhD · Sub investigator
    Recruiting
  • Hospital de Vila Franca de Xira / ULS Estuário do Tejo
    Lisbon, Lisbon District, Portugal
    • João Gonçalves Pereira, MD PhD · Contact · joaogpster@gmail.com · 351 263 006 500
    • João Gonçalves Pereira, MD PhD · Principal investigator
    • André Oliveira, MD PhD · Sub investigator
    Recruiting
  • Hospital Garcia de Orta / ULS Almada-Seixal
    Lisbon, Lisbon District, Portugal
    • Antero Fernandes, MD PhD · Contact · antevafe@gmail.com · 351 212 940 294
    • Antero Fernandes, MD PhD · Principal investigator
    • Rui Gomes, MD PhD · Sub investigator
    Recruiting
  • Hospital Prof. Doutor Fernando Fonseca / ULS Amadora -Sintra
    Lisbon, Lisbon District, Portugal
    • Paulo Teles Freitas, MD PhD · Contact · ptf@netcabo.pt · 351 214 348 200
    • Paulo Teles Freitas, MD PhD · Principal investigator
    • Tiago Ramires, MD PhD · Sub investigator
    • Cristiana Gonçalves, MD PhD · Sub investigator
    Recruiting
  • Hospital Santa Maria / ULS Santa Maria
    Lisbon, Lisbon District, Portugal
    Recruiting
  • Hospital São Francisco Xavier / Centro Hospitalar de Lisboa Ocidental
    Lisbon, Lisbon District, Portugal
    • Pedro Póvoa, MD PhD · Contact · pedrorpovoa@gmail.com · 351 210 431 000
    • Pedro Póvoa, MD PhD · Principal investigator
    • João Frutuoso, MD PhD · Sub investigator
    Recruiting
  • Hospital de VIla Nova de Gaia-Espinho / ULS Gaia e Espinho
    Vila Nova de Gaia, Porto District, Portugal
    Not yet recruiting
07

References and documents

Publications

  • Fuest KE, Ulm B, Daum N, Lindholz M, Lorenz M, Blobner K, Langer N, Hodgson C, Herridge M, Blobner M, Schaller SJ. Clustering of critically ill patients using an individualized learning approach enables dose optimization of mobilization in the ICU. Crit Care. 2023 Jan 3;27(1):1. doi: 10.1186/s13054-022-04291-8. PubMed 36597110 ↗
  • Shaw M, Viglianti EM, McPeake J, Bagshaw SM, Pilcher D, Bellomo R, Iwashyna TJ, Quasim T. Timing of Onset, Burden, and Postdischarge Mortality of Persistent Critical Illness in Scotland, 2005-2014: A Retrospective, Population-Based, Observational Study. Crit Care Explor. 2020 Apr 29;2(4):e0102. doi: 10.1097/CCE.0000000000000102. eCollection 2020 Apr. PubMed 32426744 ↗
  • Voiriot G, Oualha M, Pierre A, Salmon-Gandonniere C, Gaudet A, Jouan Y, Kallel H, Radermacher P, Vodovar D, Sarton B, Stiel L, Brechot N, Preau S, Joffre J; la CRT de la SRLF. Chronic critical illness and post-intensive care syndrome: from pathophysiology to clinical challenges. Ann Intensive Care. 2022 Jul 2;12(1):58. doi: 10.1186/s13613-022-01038-0. PubMed 35779142 ↗
  • Inoue S, Hatakeyama J, Kondo Y, Hifumi T, Sakuramoto H, Kawasaki T, Taito S, Nakamura K, Unoki T, Kawai Y, Kenmotsu Y, Saito M, Yamakawa K, Nishida O. Post-intensive care syndrome: its pathophysiology, prevention, and future directions. Acute Med Surg. 2019 Apr 25;6(3):233-246. doi: 10.1002/ams2.415. eCollection 2019 Jul. PubMed 31304024 ↗
  • Pereira RA, Sousa M, Cidade JP, Melo L, Lopes D, Ventura S, Aragao I, Lima Neto RMF, Molinos E, Marques A, Cardoso N, Marino F, Monteiro FB, Oliveira AP, Silva RC, Real AMN, Banheiro BS, Reis R, Adao-Serrano M, Cracium A, Valadas A, Ribeiro JM, Povoa P, Tapadinhas C, Mendes V, Coelho L, Maia R, Freitas PT, Ferreira IA, Ramires T, Val-Flores LS, Cascao M, Alves R, Rodeia SC, Barrigoto C, Cardiga R, Silva MJFD, Vale B, Fonseca T, Rios AL, Camoes J, Perez D, Cabral S, Ribeiro MI, Mendes JJ, Gouveia J, Fernandes SM. What changed between the peak and plateau periods of the first COVID-19 pandemic wave? A multicentric Portuguese cohort study in intensive care. Rev Bras Ter Intensiva. 2022 Oct-Dec;34(4):433-442. doi: 10.5935/0103-507X.20210037-pt. Epub 2023 Mar 3. PubMed 36888823 ↗
  • Livingston E, Bucher K. Coronavirus Disease 2019 (COVID-19) in Italy. JAMA. 2020 Apr 14;323(14):1335. doi: 10.1001/jama.2020.4344. No abstract available. PubMed 32181795 ↗
  • Cadd M, Nunn M. An A-E assessment of post-ICU COVID-19 recovery. J Intensive Care. 2021 Mar 20;9(1):29. doi: 10.1186/s40560-021-00544-w. PubMed 33743819 ↗
  • Gupta E, Jacobs MD, George G, Roman J. Beyond the ICU: Frailty and Post-ICU Disability. Healthcare Use after Acute Respiratory Distress Syndrome and Severe Sepsis. Am J Respir Crit Care Med. 2019 Apr 15;199(8):1028-1030. doi: 10.1164/rccm.201805-0928RR. No abstract available. PubMed 30849230 ↗
  • COVID-ICU Group on behalf of the REVA Network and the COVID-ICU Investigators. Clinical characteristics and day-90 outcomes of 4244 critically ill adults with COVID-19: a prospective cohort study. Intensive Care Med. 2021 Jan;47(1):60-73. doi: 10.1007/s00134-020-06294-x. Epub 2020 Oct 29. PubMed 33211135 ↗
  • Yildirim S, Durmaz Y, San Y, Taskiran I, Cinleti BA, Kirakli C. Cost of Chronic Critically Ill Patients to the Healthcare System: A Single-center Experience from a Developing Country. Indian J Crit Care Med. 2021 May;25(5):519-523. doi: 10.5005/jp-journals-10071-23804. PubMed 34177170 ↗
  • Span LF, Hermus AR, Bartelink AK, Hoitsma AJ, Gimbrere JS, Smals AG, Kloppenborg PW. Adrenocortical function: an indicator of severity of disease and survival in chronic critically ill patients. Intensive Care Med. 1992;18(2):93-6. doi: 10.1007/BF01705039. PubMed 1613205 ↗
  • Harrison DA, Creagh-Brown BC, Rowan KM. Timing and burden of persistent critical illnessin UK intensive care units: An observational cohort study. J Intensive Care Soc. 2023 May;24(2):139-146. doi: 10.1177/17511437211047180. Epub 2021 Nov 5. PubMed 37260430 ↗
  • Zhou Q, Qian H, Yang A, Lu J, Liu J. CLINICAL AND PROGNOSTIC FEATURES OF CHRONIC CRITICAL ILLNESS/PERSISTENT INFLAMMATION IMMUNOSUPPRESSION AND CATABOLISM PATIENTS: A PROSPECTIVE OBSERVATIONAL CLINICAL STUDY. Shock. 2023 Jan 1;59(1):5-11. doi: 10.1097/SHK.0000000000002035. Epub 2022 Nov 17. PubMed 36383370 ↗

Individual participant data

Plan to share: Yes — Individual participant data collected in this study will be made available to other researchers. All data will undergo a thorough anonymization process prior to sharing to prevent direct or indirect identification of participants. Each patient will be assigned an internal numeric code, consisting of two digits representing the center of origin and four sequential digits assigned by order of admission. No personal identifiers (e.g., name, national ID number, full date of birth, address) are collected. The anonymized dataset will be accompanied by a data dictionary, describing each variable and its format, to allow full interpretation and reuse of the data. This approach ensures participant confidentiality and complies with ethical and legal requirements, while enabling secondary analyses, replication studies, or meta-analyses by other researchers.

Supporting information: Study protocol, Sap

08

Registry details

Key details

Study ID
NCT07510776
Lead sponsor
Lisbon Academic Medical Center - Centro Académico de Medicina de Lisboa
Collaborators
Centro Hospitalar de Vila Nova de Gaia/Espinho, Hospital Prof. Doutor Fernando Fonseca, Unidade Local de Saúde Almada-Seixal, Centro Hospitalar Lisboa Ocidental, Hospital Vila Franca de Xira, Centro Hospitalar De São João, E.P.E.
Responsible party
Susana Mendes Fernandes (Prof. Dr., Lisbon Academic Medical Center - Centro Académico de Medicina de Lisboa) — Principal investigator
First posted
Apr 3, 2026
Start date
Jan 13, 2025
Primary completion
Dec 31, 2026 (estimated)
Completion
Dec 31, 2027 (estimated)
Last update
Apr 13, 2026

Study contacts

Susana Fernandes, MD PhD.
Contact
susanamfernandes@medicina.ulisboa.pt
351 21 798 5100
Mariana Santos, PhD
Contact
marianamsantos@medicina.ulisboa.pt
351 21 798 5100
Susana Fernandes, MD PhD
principal investigator · Lisbon School of Medicine

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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