Comparison of Short Peptide and Whole Protein Formula in the Early Enteral Nutrition of Patients With Sepsis

Comparison of Short Peptide and Whole Protein Formula in the Early Enteral Nutrition of Patients With Sepsis: a Single-Center, Prospective, Randomized Controlled Study

To explore the effects of early enteral nutrition with short peptide formula on energy metabolism and clinical outcomes in patients with sepsis based on blood samples, clinical database, full-spectrum metabolomics test and imaging data, and to form a theoretical basis for optimizing the formula of early enteral nutrition in patients with sepsis.

Study Overview

• Status: Not yet recruiting
• Conditions: Sepsis; Nutrition
• Intervention / Treatment: Dietary supplement: Short peptide enteral nutrition; Dietary supplement: Whole protein enteral nutrition

Detailed Description

This study is a single-center prospective trial. Based on the annual patient volume, available human resources, and funding at our research center, the expert team determined a sample size of 80 cases, with 40 cases in the experimental group and 40 in the control group. Eligible participants will be randomized 1:1 via computer-generated randomization into two groups, receiving either a short-peptide-based enteral nutrition formula or a whole-protein-based enteral nutrition formula.

Short-peptide formula group:

Within 48 hours of ICU admission, short-peptide-based enteral nutrition (Peptisorb) will be initiated. For patients with impaired swallowing or unconsciousness, a nasogastric tube will be placed. Feeding will start with low-calorie or trophic feeding, reaching 70% of the target energy and 1.2-1.5 g/kg/day of protein within 7 days. Due to significant individual variability in energy expenditure among sepsis patients, indirect calorimetry (IC) will be used to measure energy needs. If IC is unavailable, a weight-based formula (20-25 kcal/kg/day) will be applied. If patients remain in the ICU after 7 days, feeding will be gradually increased to full energy and protein targets as tolerated, followed by a transition to whole-protein nutrition.

Whole-protein formula group:

Within 48 hours of ICU admission, whole-protein-based enteral nutrition (Nutrison) will be initiated, with the remaining protocol identical to the short-peptide group.

The study will assess changes in metabolomics after 7 days of early enteral nutrition with different protein formulations in sepsis patients, as well as differences in nutritional status, biochemical markers, and short- and long-term clinical outcomes.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yanni Zhang, MD, PhD; Phone Number: +86 13381819621; Email: yanni99@126.com
• Study Contact Backup: Name: JieQiong Song, MD, PhD; Phone Number: +86 13917056745; Email: song.jieqiong@zs-hospital.sh.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Informed consent has been signed
2. Aged from 18 to 80 years old
3. Within 24 hours after admission to ICU
4. Sepsis was diagnosed according to the 2016 International Sepsis 3.0 diagnostic criteria
5. Without gastrointestinal perforation, bleeding, obstruction and other contraindications to enteral nutrition
6. Expected ICU stay for more than 7 days

Exclusion Criteria:

1. Receiving palliative care or expected to die within 72 hours
2. Pregnant or breastfeeding
3. Use of high dose vasopressor maintenance (norepinephrine dosage > 0.5 μg/kg/min)
4. Requiring restricted protein intake or additional protein supplementation (e.g., patients with hepatic encephalopathy, severe renal insufficiency, severe burns, severe malnutrition, etc..)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Short peptide formula; Within 48 hours of ICU admission, short-peptide-based enteral nutrition (Peptisorb) will be initiated. For patients with impaired swallowing or unconsciousness, a nasogastric tube will be placed. Feeding will start with low-calorie or trophic feeding, reaching 70% of the target energy and 1.2-1.5 g/kg/day of protein within 7 days. Due to significant individual variability in energy expenditure among sepsis patients, indirect calorimetry (IC) will be used to measure energy needs. If IC is unavailable, a weight-based formula (20-25 kcal/kg/day) will be applied. If patients remain in the ICU after 7 days, feeding will be gradually increased to full energy and protein targets as tolerated, followed by a transition to whole-protein nutrition.	Dietary supplement: Short peptide enteral nutrition; Short peptide formula enteral nutrition was initiated within 48 hours after admission to the ICU. For patients with poor swallowing function or no consciousness, nasogastric tubes were placed. Starting from low-calorie or nourishing feeding, 70% of the target energy should be achieved within 7 days, and the protein should be 1.2-1.5 g/kg/d. Due to the large individual differences in energy expenditure among patients with sepsis, the indirect calorimetry (IC) method was used to determine energy expenditure. If the IC method is not feasible, the calculation formula based on body weight: 20-25 kcal/kg/d should be applied for calculation. If the patient is not transferred out of the ICU after 7 days, continue to gradually increase to the target energy and protein requirements under tolerable conditions, and gradually transition to whole protein nutrition after 7 days.
Active Comparator: Whole protein formula; Within 48 hours of ICU admission, whole-protein-based enteral nutrition (Nutrison) will be initiated, with the remaining protocol identical to the short-peptide group.	Dietary supplement: Whole protein enteral nutrition; The whole protein formula enteral nutrition was initiated within 48 hours of admission to the ICU, and the rest were same.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolomics changes form	Key assessments include: ① Concentration changes of differential metabolites in core pathways (BCAA, SCFA, bile acid metabolism); ② Correlation between metabolite fluctuations and nutritional markers (albumin, prealbumin); ③ Predictive modeling linking metabolic signatures to clinical outcomes (infection rate, ICU LOS). The above data were all normalized and ultimately presented in the form of a heatmap.	On the 7th day after enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality at 90 days		90 days
Daily average protein intake	Daily average protein intake, including EN, PN, IVAA, and measurable oral protein supplements; oral diets with unquantifiable protein content excluded (Unit: g).	7 days
Daily average energy intake	Daily average energy intake (Unit: g).	7 days
Energy adequacy rate	Energy adequacy rate on the 3rd and 7th day after enrollment (Unit: %).	On the 3rd and 7th day after enrollment
Inflammatory markers	Including C-reactive protein (CRP) (Unit: mg/L), White blood cell count (WBC) (Unit: *10^9/L), and Neutrophil count (Neut#) (Unit: *10^9/L).	7 days
Nutritional status	Albumin (Alb) (Unit: g/L) and Pre-albumin (PA) (Unit: mg/L).	7 days
Liver function	Bilirubin (BIL) (Unit: μmol/L)	7 days
Renal function	Blood urea nitrogen (BUN) (Unit: mmol/L) and Serum creatinine (Cr) (Unit: umol/L).	7 days
Enteral nutritional tolerance rate	Manifestations of enteral nutrition intolerance: Gastric retention (gastric residual volume > 500 mL within 4 hours) Severe nausea or vomiting; Abdominal distension; Diarrhea (≥ 3 bowel movements per day with loose stools, Bristol Stool Scale type 5-7); Hematochezia leading to hemodynamic instability.	7 days
Skeletal muscle depletion condition	A single cross-sectional image at the L3 level was obtained via CT scan. Skeletal muscle was identified and quantified within the image using Hounsfield Unit (HU) thresholds of -29 to +150. The total muscle area at this level was calculated using ImageJ image analysis software. After normalization by the square of height (m²), the third lumbar skeletal muscle index (L3-SMI) was derived.	7 days
Days of ventilator use		28 days
28-day all-cause mortality rate		28 days

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): June 25, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: May 12, 2025
• First Submitted That Met QC Criteria: June 25, 2025
• First Posted (Actual): June 26, 2025

Study Record Updates

• Last Update Posted (Actual): June 26, 2025
• Last Update Submitted That Met QC Criteria: June 25, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia
• Other Study ID Numbers: B2025-213R

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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