Clinical trial NCT06344546: Metabolic Pathway Analysis in Intensive Care Unit Patients With Refeeding Syndrome
Official title: Metabolic Pathway Analysis in Refeeding Syndrome: a Nested Explorative Metabolomics Substudy of the GUTPHOS Multicenter Observational Study (GUTPHOS-Metabolomics)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Critical Illness
Refeeding Syndrome
Hypophosphatemia
Lead sponsor: Karolinska University Hospital
Sponsor class: OTHER
Collaborators: name: Foggia Hospital
name: Faculty Hospital Kralovske Vinohrady
First posted: 2024-04-03
Enrollment: 218
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients admitted to the intensive care unit.

Brief summary: The overall aim of the study is to improve understanding of refeeding syndrome (RFS) in patients admitted to the intensive care unit (ICU) using metabolomics. Patients are included as part of a prospective multicenter observational study on phosphate disorders in the ICU. Blood samples are collected day 1-7 of ICU stay. Samples from patients who develop refeeding hypophosphatemia and matched controls without hypophosphatemia are analysed for metabolomics and proteomics. Untargeted analyses will be performed to identify the affected metabolic pathways. The investigators will also perform AUROC analyses to identify potential biomarkers for early detection of RFS.

Detailed description: A nested case-control study situated within GUTPHOS Part B: A prospective, multicenter non-interventional cohort study investigating the incidence of abnormal phosphate levels and associated outcomes in adult patients admitted to the ICUs of participating sites. Inclusion/exclusion criteria for GUTPHOS Part B are described in the separate study protocol.

At sites participating in the nested substudy, an additional 2 ml EDTA blood sample is drawn once daily in all patients included in GUTPHOS Part B from ICU admission up to a maximum of calendar day 7 in ICU. The sampling for metabolomics analysis should be performed in close proximity with daily routine blood tests, and always before treatment of hypophosphatemia with phosphate supplementation or restricted nutritional intake. Plasma samples are obtained through centrifugation within 20 minutes and frozen to -80 degrees Celcius within 60 minutes until analysis. The timing and handling of samples according to standard operating procedures will be documented on a separate case report form.

In ICU patients diagnosed with refeeding hypophosphatemia, comprehensive metabolomic profiling is performed in the plasma sample from ICU admission and the sample drawn in conjunction to the blood phosphate measurement diagnostic of RH.

Cases with RH are matched in a 1:1 ratio to ICU patients without RH. Controls are matched according to sex, age, illness severity on admission and energy delivery (kcal/kg adjusted body weight) in the 24 hours preceding the diagnosis of RH.

Refeeding hypophosphatemia is defined as new onset hypophosphatemia (\<0.65 mmol/L) within 72 hours from the start of medical nutrition therapy, with a drop of \>0.16 mmol/L from any previous Pi value during ICU stay and where no other likely cause of hypophosphatemia is present.

Eligibility criteria: Inclusion Criteria:

* Admission to ICU during the study period
* Age ≥18 years

Exclusion Criteria:

* Age \<18 years
* Patients with restrictions of care such as "no intubation" or "no renal replacement therapy" on ICU admission and patients admitted for treatment as organ donors
* Continuous chronic home ventilation for neuromuscular disease;
* Declined participation or informed consent (if the local ethics committee requests the latter for this non-interventional study);
* Readmission to ICU during the study period

Primary outcomes:
measure: Metabolomics
timeFrame: Onset of RFS, within the first 7 days in ICU.
Secondary outcomes:
measure: Metabolomics
timeFrame: Prior to onset of RFS, within the first 7 days in ICU.
Other outcomes:
Locations:
city: Prague
country: Czechia
facility: University Hospital Královské Vinohrady
city: Foggia
country: Italy
facility: University Hospital Policlinico of Foggia
city: Huddinge
country: Sweden
facility: Karolinska University Hospital
state: Stockholm
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset Solna
Study officials:
affiliation: Karolinska University Hospital
name: Olav Rooyackers, PhD
role: STUDY_CHAIR
References: