Heterogeneity of Critical Illness: a Cohort Study (HEALICS)

Heterogeneity of Critical Illness: Exploring New Risk Factors for Severity of Disease in Intensive Care Patients. A Cohort Study

Rationale: There is large heterogeneity in disease states of critically ill patients at ICU admittance and there is also large heterogeneity in their disease severity during ICU stay. Still, some patients may show remarkable similarities in disease patterns. There is a lack of understanding of causal mechanisms that lead to divergent outcomes in critically ill patients, and at the same time different diseases may share common underlying, yet unidentified, causal pathways that could explain similarities between different diseases.

Objective: To explore the association between patient characteristics and the severity of organ failure in critically ill patients admitted to the ICU Study design: Prospective cohort study Study population: Adult critically ill patients in the ICU Intervention (if applicable): not applicable Main study parameters/endpoints: Maximum severity of organ failure observed during ICU stay measured by the maximum SOFA score and quality of life at one year follow-up

Study Overview

• Status: Recruiting
• Conditions: Critically Ill; Organ Failure, Multiple
• Intervention / Treatment: Diagnostic test: Standard diagnosis test

Detailed Description

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: <All patients will undergo physical examination, including ultrasound evaluation upon ICU admission according to standard practice care. The burden will be a blood sample (and urine sample) at admission. Blood sample will be obtained by arterial line (or venous access) which is part of standard ICU care. So there will be no additional puncture for this study. Collection of variables during ICU stay will all be either part of standard clinical care or include extra physical examination or ultrasound evaluation. For follow-up patients will be evaluated by phone at 6 months and at 12 months by home-visit. This is also already part of the investigator's evaluation of quality of care. Except for blood sampling, all study related procedures have previously been approved by the Institutional Review Board (IRB). The patient will experience no individual benefit.

• Study Type: Observational
• Enrollment (Estimated): 5000

Contacts and Locations

• Study Contact: Name: Fredrike Zwiers, PhD; Phone Number: +31 503619838; Email: f.zwiers-blokzijl@umcg.nl

Study Locations

• Netherlands
  • Provincie Groningen
    • Groningen, Provincie Groningen, Netherlands, 9713GZ
      • Recruiting
      • University Medical Center Groningen
      • Contact: Fredrike Zwiers, PhD; Phone Number: 0503619838; Email: f.zwiers-blokzijl@umcg.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All patients acutely admitted to the ICU

Description

Inclusion Criteria:

• Adults Definition: age ≥18 years.
• Emergency admission to the ICU Definition: patients who are acutely admitted to the ICU due to acute or unexpected critical illness, either from the emergency department or the ward or transferred from an ICU (or a ward) from another hospital.

Exclusion Criteria:

• Planned admission
• Absence of an invasive arterial or venous line for blood sampling.
• Any continued cardiopulmonary resuscitation efforts upon admission which limit access to the patient for research activities.
• Main ICU admission reason chronic (non-invasive) home ventilation
• Main ICU admission reason normothermic treatment after cardiac arrest
• Main ICU admission reason ischemic stroke, intracerebral bleeding, or isolated neurotrauma
• Main ICU admission reason Coronavirus Disease 2019 (COVID-19)
• Solid organ or hematopoietic stem cell transplant during current hospital admission
• Strict isolation due to any contagious disease
• No informed consent

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Adult critically ill patients in the ICU; Acutely admitted to the ICU	Diagnostic test: Standard diagnosis test; Care as usual

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of organ failure observed during ICU stay	The primary prognostic outcome will be the maximum SOFA score during ICU stay. The daily maximum SOFA score will be considered up to a maximum of 90 days.	During ICU admission with a maximum of 90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Follow-up Quality of life data	Patients will be evaluated by questionnaires at 6 and 12 months follow-up.Follow-up data will include survival status and data on quality of life.; Patients psychological functioning will be evaluated using the Short Form 20 and the Hospital Anxiety and Depression Scale (HADS).; Patients physical functioning data will be measured by the KATZ ADL index and the Clinical Frailty Score. In addition, the Euro-Qol (EQ-5d) will be used.; Social functioning data will be collected using the General Functioning 6 scale (GF6) which is a subscale of the GF12 and is a quick and effective tool to assess the overall functioning of families. Data will be collected from both patients and family members. Return to work will only be evaluated at 12 months follow-up by 4 extra questions concerning the patients return to work. In addition we will explore and validate extended modifications on the total and domain level of the organ failure assessment score (SOFA+).	6 and 12 months after ICU discharge

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Investigators: Principal Investigator: Frederik Keus, PhD, University Medical Center Groningen

Publications and helpful links

General Publications

• van der Aart TJ, Luxen M, Koeze J, Londen MV, Hackl M, Ter Maaten JC, van Meurs M, Bouma HR; the Acutelines research group. Validation of plasma microRNAs as biomarkers in sepsis associated acute kidney injury upon first clinical presentation reveals limited diagnostic and prognostic performance. PLoS One. 2025 Sep 4;20(9):e0331442. doi: 10.1371/journal.pone.0331442. eCollection 2025.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): January 1, 2030

Study Registration Dates

• First Submitted: July 27, 2020
• First Submitted That Met QC Criteria: August 4, 2020
• First Posted (Actual): August 6, 2020

Study Record Updates

• Last Update Posted (Actual): May 26, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Shock; Pathological Conditions, Signs and Symptoms; Critical Illness; Multiple Organ Failure
• Other Study ID Numbers: 202000405

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: On request
• IPD Sharing Time Frame: In two years
• IPD Sharing Access Criteria: On request
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No