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

Not Applicable

Recruiting

• Conditions: Critically Ill
• Interventions: Dietary Supplement: Enteral protein supplementation

• Registration Number: NCT04565613
• Lead Sponsor: KK Women's and Children's Hospital

Brief Summary

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).

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 Timeline

• Study First Submitted: 2020-09-15
• Study First Submitted QC: 2020-09-22
• Study First Posted: 2020-09-25
• Study Start: 2021-01-25
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-18
• Last Update Posted: 2024-03-19
• Primary Completion: 2024-09
• Study Completion: 2025-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 70

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Study interventional group	Enteral protein supplementation	The participants will receive protein supplementation to reach a final goal of 1.5 g/kg/day of protein on full feeds.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

National University Hospital; 🇸🇬 Singapore, Singapore