Protein Supplementation vs Standard Feeds in Underweight Critically Ill Children: A Dual-Centre Pilot RCT

Protein Supplementation Versus Standard Feeds in Underweight Critically Ill Children: A Dual-Centre Randomized Controlled Pilot Trial

This pilot trial is part of a long-term research program leading to a large trial to determine if a strategy of supplementing protein in a subset of critically ill children is superior to standard enteral nutrition care. The investigators hypothesize that protein supplementation to critically ill children with body mass index (BMI) z-score <0 reduces the length of stay in the paediatric intensive care unit (PICU) and hospital, as well as the duration of mechanical ventilation (MV).

Study Overview

• Status: Recruiting
• Conditions: Critically Ill
• Intervention / Treatment: Dietary supplement: Enteral protein supplementation

Detailed Description

Protein malnutrition is prevalent among critically ill children and associated with poor clinical outcomes. Current guidelines for provision of protein in daily management of critically ill children in pediatric intensive care units (PICUs) are based on limited and not high-quality evidence. The current protein supplementation approach, "one-size-fits-all" nutrition prescription, may not be appropriate for every critically ill child. Given the heterogeneity of the patients admitted to the PICU, a targeted approach based on individuals' needs represents a potential advancement in PICU care.

The central hypothesis is that protein supplementation in PICU care leads to improved clinical outcomes in subgroups of patients only. The investigators propose a dual-centre pilot randomized controlled trial in Singapore with two major aims:

1. To obtain key information for planning and conducting a large-scale multicentre study in Asia; and
2. to evaluate the benefit of protein supplementation to critically ill children with body mass index (BMI) z-scores on PICU <0

The main clinical outcome of interest is total number of days of hospital stay (from PICU admission to hospital discharge). Two protein supplementation regimes (≥ 1.5g/kg/day vs. standard care) will be randomly allocated to PICU patients with body mass index (BMI) z-scores <0. The investigators will determine the effect of protein supplementation on total length of hospital stay and other clinical outcomes, and assess the impact of protein supplementation on acquired functional impairment of PICU survivors 6 months after hospital discharge. In addition, the investigators will explore whether muscle ultrasound is a biomarker for protein balance in pediatric critical illness.

Upon completion of this study, the investigators will have strong preliminary data to plan, refine their study approach, and execute a future large multi-centre study across Asia. These data will ultimately guide protein provision and nutritional management of patients in PICU setting.

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jan Hau Lee; Phone Number: 63926347; Email: lee.jan.hau@singhealth.com.sg

Study Locations

• Singapore
  • Singapore, Singapore, 119228
    • Recruiting
    • National University Hospital
    • Contact: Jacqueline Ong; Phone Number: 6567725876; Email: jacqueline_ong@nuhs.com.sg
    • Principal Investigator: Jacqueline Ong

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 weeks to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Between 28 days and 18 years of age
2. Have a BMI z-score < 0 on PICU admission
3. Requires respiratory support in the form of invasive or non-invasive mechanical ventilation (CPAP or BiPAP) within 24-48 hours of PICU admission, and the attending physician expects the child to require any respiratory support for at least 48 hours of PICU admission
4. Requires enteral nutrition support for feeding (e.g., oro-gastric, nasogastric, gastrostomy, naso-jejunal, oro-jejunal)
5. Have an expected PICU stay of > 48 hours

Exclusion Criteria:

1. Are not expected to survive this PICU admission because of palliative care (e.g., do-not-resuscitate status) or limited life support
2. Progressive neuromuscular disease (e.g., spinal muscular atrophy, Duchenne or other muscular dystrophy, multiple sclerosis, amyotrophic lateral sclerosis)
3. Medical conditions where increased or decreased protein intake is required, including acute kidney injury (stage 3 KDIGO criteria), chronic kidney disease (stage 4 and 5), inborn errors of metabolism, fulminant liver failure, severe burn injury
4. Contraindications to enteral nutrition (e.g., gut hemorrhage, post-gastrointestinal surgery etc.)
5. Diagnosed cow's milk protein allergy
6. Parenteral nutrition
7. Premature infants who are less than corrected gestational age of 44 weeks (gestational age + weeks after birth)
8. Were previously enrolled in this trial
9. Are currently enrolled in a potentially confounding trial
10. Diagnosis of anorexia nervosa and other eating disorders
11. On extra-corporeal membrane oxygenation (ECMO) support
12. Conditions that required significant fluid restriction (≤75% of maintenance fluid) (e.g., post cardiac surgery etc.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard care group; The participants will receive feeding as per standard of care (without protein or any other supplementations).
Experimental: Study interventional group; The participants will receive protein supplementation to reach a final goal of 1.5 g/kg/day of protein on full feeds.	Dietary supplement: Enteral protein supplementation; The participants in the study interventional group will receive protein supplementation to reach a final goal of 1.5 g/kg/day of protein on full feeds. This will be via 100% whey protein isolate (Nestle Beneprotein). Doses will be calculated on the patient's admission weight and rounded up to the nearest 1g. Doses will not be adjusted to account for weight changes in the PICU. Protein supplementation will continue for a total of 7 days from the start of enrolment into the study or until PICU discharge, whichever is earlier. If the patient is able to take solid feeds during the study intervention period, the intervention will be stopped. However, if the device required for feeding is removed but the patient takes milk/liquid feeds fully, protein supplementation will continue.; Other Names: Protein isolate (Nestle Beneprotein)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of eligible patients approached for consent	Number of eligible patients who are approached for consent	Throughout study period, over 36 months
Proportion of participants receiving their first protein supplementation within 72 hours of enrolment	Number of patients who received protein supplementation within 72 hours of enrolment	Throughout the study, over 24 months
Participant accrual rate	Average monthly enrolment at each centre	Throughout the study, over 24 months
Protocol adherence	>80% of protein target administered according to the protocol in the intervention arm	Throughout study period, over 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PICU mortality	Death in PICU	Throughout study period, over 36 months
PICU length of stay	Duration of stay in the PICU	Throughout study period, over 36 months
Hospital length of stay	Duration of stay in the hospital	Throughout the study period, over 36 months
Adverse events	Development of adverse events such as feeding intolerance, diarrhoea, gastrointestinal bleeding	Throughout study period, over 36 months
Change in muscle size	Longitudinal change in muscle size as assessed by ultrasound. Muscles for assessment include rectus femoris and diaphragm	During PICU stay, PICU discharge, hospital discharge and 6 months follow-up
Anthropometry	Change in anthropometric measurements	During PICU stay, PICU discharge, hospital discharge and 6 months follow-up
Functional status	Assessment of functional status via functional status scale (FSS). FSS scores ranged from 6 to 30. A higher score denotes worse outcome	PICU admission, hospital discharge and 6 months follow-up

Collaborators and Investigators

• Sponsor: KK Women's and Children's Hospital
• Collaborators: National Medical Research Council (NMRC), Singapore; Duke-NUS Graduate Medical School; Singapore Clinical Research Institute
• Investigators: Principal Investigator: Jan Hau Lee, KK Women's and Children's Hospital, SingHealth

Publications and helpful links

General Publications

• Wong JJM, Ong JSM, Ong C, Allen JC, Gandhi M, Fan L, Taylor R, Lim JKB, Poh PF, Chiou FK, Lee JH. Protein supplementation versus standard feeds in underweight critically ill children: a pilot dual-centre randomised controlled trial protocol. BMJ Open. 2022 Jan 4;12(1):e047907. doi: 10.1136/bmjopen-2020-047907.

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2021
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: September 15, 2020
• First Submitted That Met QC Criteria: September 22, 2020
• First Posted (Actual): September 25, 2020

Study Record Updates

• Last Update Posted (Actual): March 19, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Nutrition; Protein supplementation; Critically ill
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Body Weight; Critical Illness; Thinness
• Other Study ID Numbers: 2020/2742

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data from this pilot study may be used for the larger study. If so, these data will not be made available to other researchers till the larger study is completed or deemed not feasible.

Drug and device information, study documents

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