Clinical trial NCT04565613: Protein Supplementation vs Standard Feeds in Underweight Critically Ill Children: A Dual-Centre Pilot RCT
Official title: Protein Supplementation Versus Standard Feeds in Underweight Critically Ill Children: A Dual-Centre Randomized Controlled Pilot Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Critically Ill
Keywords: Critically ill
Protein supplementation
Nutrition
Lead sponsor: KK Women's and Children's Hospital
Sponsor class: OTHER_GOV
Collaborators: name: Duke-NUS Graduate Medical School
name: Singapore Clinical Research Institute
name: National Medical Research Council (NMRC), Singapore
First posted: 2020-09-25
Enrollment: 70
Sex: ALL
Minimum age (years): 28
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized to enteral protein supplementation or standard care (no enteral protein supplementation) in a 1:1 ratio.
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: 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.)

Primary outcomes:
measure: Proportion of eligible patients approached for consent
timeFrame: Throughout study period, over 36 months
measure: Proportion of participants receiving their first protein supplementation within 72 hours of enrolment
timeFrame: Throughout the study, over 24 months
measure: Participant accrual rate
timeFrame: Throughout the study, over 24 months
measure: Protocol adherence
timeFrame: Throughout study period, over 24 months
Secondary outcomes:
measure: PICU mortality
timeFrame: Throughout study period, over 36 months
measure: PICU length of stay
timeFrame: Throughout study period, over 36 months
measure: Hospital length of stay
timeFrame: Throughout the study period, over 36 months
measure: Adverse events
timeFrame: Throughout study period, over 36 months
measure: Change in muscle size
timeFrame: During PICU stay, PICU discharge, hospital discharge and 6 months follow-up
measure: Anthropometry
timeFrame: During PICU stay, PICU discharge, hospital discharge and 6 months follow-up
measure: Functional status
timeFrame: PICU admission, hospital discharge and 6 months follow-up
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: National University Hospital
Study officials:
affiliation: KK Women's and Children's Hospital, SingHealth
name: Jan Hau Lee
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.