Metabolic Pathway Analysis in Intensive Care Unit Patients With Refeeding Syndrome

Completed

• Conditions: Critical Illness; Refeeding Syndrome; Hypophosphatemia
• Interventions: Diagnostic Test: Metabolomics

• Registration Number: NCT06344546
• Lead Sponsor: Karolinska University Hospital

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.

Study Timeline

• Study First Submitted: 2024-03-07
• Study First Submitted QC: 2024-03-27
• Study Start: 2024-04-01
• Study First Posted: 2024-04-03
• Primary Completion: 2024-06-02
• Study Completion: 2024-06-02
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-27
• Last Update Posted: 2025-04-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 218

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Refeeding hypophosphatemia	Metabolomics	ICU patients who fulfill diagnostic criteria for refeeding hypophosphatemia.
Controls	Metabolomics	ICU patients without refeeding hypophosphatemia. Controls selected to match for sex, age, severity of illness and nutritional delivery prior to refeeding hypophosphatemia.

Primary Outcome Measures

Name	Time	Method
Metabolomics	Onset of RFS, within the first 7 days in ICU.	The plasma metabolome (\>300 metabolites related to cell metabolism) will be characterized by mass spectroscopy from blood samples taken at the onset of refeeding syndrome (RFS) and analyzed for specific alterations in metabolic pathways associated with RFS in an untargeted approach.

Secondary Outcome Measures

Name	Time	Method
Metabolomics	Prior to onset of RFS, within the first 7 days in ICU.	Potential biomarkers in the plasma metabolome (\>300 metabolites related to cell metabolism) associated with the development of refeeding syndrome (RFS) will be identified through principal component analysis and ROC curve analysis.

Trial Locations

Locations (4)

University Hospital Královské Vinohrady; 🇨🇿 Prague, Czechia

University Hospital Policlinico of Foggia; 🇮🇹 Foggia, Italy

Karolinska University Hospital; 🇸🇪 Huddinge, Stockholm, Sweden

Karolinska Universitetssjukhuset Solna; 🇸🇪 Stockholm, Sweden