Comparing High-protein Vs. Standard Protein Nutritional Support in Critically Ill Patients At Risk for Refeeding Syndrome

Comparing the Effects of High-protein Nutritional Support with Standard Protein Nutritional Support Through the Administration of Whey Protein Supplements on Clinical Outcomes of Critically Ill Patients At Risk for Refeeding Syndrome: a Randomized Comparative Clinical Trial

The goal of this clinical trial is to determine the optimal protein administration strategy for enhancing both nutritional and clinical outcomes, as well as reducing complications and mortality in ICU patients at risk for refeeding syndrome (RS). This study will include critically ill patients at risk for RS who are receiving supportive nutrition. The primary hypothesis is that higher protein intake will lead to a decreased incidence of refeeding syndrome. It is also expected that patients receiving more protein will have better clinical outcomes, lower mortality, and shorter ICU and hospital stays.

Study Overview

• Status: Recruiting
• Conditions: Critical Illness; Malnutrition; Refeeding Syndrome; At Risk for Refeeding Syndrome
• Intervention / Treatment: Dietary supplement: Whey protein

Detailed Description

Patients will be randomly assigned to two groups: the high-protein group and the standard-protein group. Upon ICU admission, and after meeting the inclusion criteria and identifying a risk of refeeding syndrome (RS), they will be allocated to one of the two groups. Patient selection for RS risk will be based on the diagnostic criteria outlined in the 2020 ASPEN guidelines. The m-NUTRIC and APACHE II scores will be calculated for all patients at ICU admission and 24 hours before the initiation of feeding. Monitoring for multi-organ dysfunction syndrome (MODS) will involve daily laboratory tests and organ failure assessment using the SOFA score.

Before starting the nutritional intervention, all patients will receive 100 mg of thiamine daily for one week, along with a daily multivitamin-mineral supplement. Due to the risk of RS, calorie intake will begin at low levels and will be cautiously increased in both groups. To calculate the energy needs, ideal body weight will be used. In the high-protein group, the target protein intake will be 2 grams per kilogram of body weight per day, while in the standard-protein group, it will be 1.3 grams per kilogram of body weight per day. Protein will be introduced gradually, starting from a low level, as part of nutritional support, with whey protein powder added if needed as a supplement. If serum creatinine levels rise, protein powder will be removed from the patient's diet. The intervention duration will be 14 days, with a minimum of 5 days.

The primary clinical outcome is the incidence of refeeding syndrome (RS), while secondary outcomes include the occurrence of infections, hospital length of stay, ICU length of stay, multi-organ failure, and mortality within 45 days of admission. RS will be diagnosed according to the 2020 ASPEN guidelines. Serum concentrations of potassium, magnesium, phosphate, glucose, urea, and creatinine will be measured daily for one week.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Zahra Vahdat Shariatpanahi Professor; Phone Number: 0098-021-22357484; Email: nutritiondata@yahoo.com

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of
    • Recruiting
    • Ayatollah Taleghani Medical, Educational, and Therapeutic Center, Shahid Beheshti University of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Willingness to cooperate and complete the informed consent form by the patient or legal guardian;
• age ≤ 18 years and < 65 years;
• Non-pregnant and non-lactating;
• Serum creatinine ≥ 1.1 mg/dl for women and ≥ 1.2 mg/dl for men;
• No organ failure at the time of study enrollment;
• Intervention initiation within 48 hours of ICU admission;
• No history of metastatic cancer or end-stage disease;
• No absolute contraindications to enteral nutrition (e.g., persistent ileus, gastrointestinal ischemia, persistent or biliary vomiting, mechanical obstruction);
• No active infections, sepsis, severe sepsis, or septic shock;
• No intolerance to the whey protein supplement used in the current study;
• Not participating in other clinical trials concurrently with this study;
• No clinical conditions with higher or lower protein needs, such as burns, sepsis, cirrhosis, or chronic kidney disease;
• No diabetes with severe complications such as ketoacidosis, hyperosmolar coma, or acidosis.

Exclusion Criteria:

• Unwillingness to continue cooperation during study;
• Discharge or death of the patient earlier than 5 days from the start of the intervention;
• Occurrence of side effects during the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High-protein; The target protein intake of 2 grams per kilogram of body weight per day will be gradually introduced, starting at a low level, through nutritional support, with whey protein powder added if needed as a supplement.	Dietary supplement: Whey protein; Whey protein powder will be provided with nutritional support in both groups if needed to meet the target protein intake.
Active Comparator: Standard-protein; The target protein intake of 1.3 grams per kilogram of body weight per day will be gradually introduced, starting at a low level, through nutritional support, with whey protein powder added if needed as a supplement.	Dietary supplement: Whey protein; Whey protein powder will be provided with nutritional support in both groups if needed to meet the target protein intake.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with refeeding syndrome	Refeeding syndrome will be diagnosed based on a decrease in serum levels of electrolytes, including potassium, magnesium, and phosphate, within the first 5 days of nutrition delivery.	within the first 5-7 days of nutrition delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of infection	Determining and comparing the incidence of infection and its duration	Within 5-14 days of nutrition delivery
Number of participants with organ failure as measured by SOFA score	Organ failure will be assessed using the SOFA Score (Sequential Organ Failure Assessment), which evaluates the function of the following organ systems: Cardiovascular Respiratory Renal Hepatic Coagulation Neurological	Within 5-14 days of nutrition delivery
Duration of ICU stay		up to 7 weeks after admission
Duration of hospital stay		up to 7 weeks after admission
Mortality	45-day mortality from the time of ICU admission	up to 45-day

Collaborators and Investigators

• Sponsor: Shahid Beheshti University
• Investigators: Principal Investigator: Zahra Vahdat Shariatpanahi Professor, School of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2025
• Primary Completion (Estimated): February 15, 2026
• Study Completion (Estimated): April 15, 2026

Study Registration Dates

• First Submitted: February 2, 2025
• First Submitted That Met QC Criteria: February 12, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 13, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: mortality; Malnutrition; Complication; Critically ill; High-protein; Refeeding syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Nutrition Disorders; Disease Attributes; Disease; Malnutrition; Syndrome; Critical Illness; Refeeding Syndrome
• Other Study ID Numbers: 450/1272

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No