Protein Supplementation in Critically Ill Children: A Dual-Centre Randomized Controlled Pilot Trial
Study Details
Study Description
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 ≤ -2 reduces the length of stay in the paediatric intensive care unit (PICU) and hospital, as well as the duration of mechanical ventilation (MV).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
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:
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To obtain key information for planning and conducting a large-scale multicentre study in Asia; and
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to evaluate the benefit of protein supplementation to critically ill children with body mass index (BMI) z-scores on PICU ≤ -2.
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 ≤ -2. 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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| No Intervention: Standard care group The participants will receive feeding as per standard of care (without protein or any other supplementations). |
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| 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:
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Outcome Measures
Primary Outcome Measures
- Proportion of eligible patients approached for consent [Throughout study period, over 36 months]
Number of eligible patients who are approached for consent
- 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
- Participant accrual rate [Throughout the study, over 24 months]
Average monthly enrolment at each centre
- Protocol adherence [Throughout study period, over 24 months]
>80% of protein target administered according to the protocol in the intervention arm
Secondary Outcome Measures
- PICU mortality [Throughout study period, over 36 months]
Death in PICU
- 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
- 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
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
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Between 28 days and 18 years of age
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Have a BMI z-score ≤ -2 on PICU admission
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Requires respiratory support in the form of invasive MV 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
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Requires enteral nutrition support for feeding (e.g., oro-gastric, nasogastric, gastrostomy, naso-jejunal, oro-jejunal)
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Have an expected PICU stay of > 48 hours
Exclusion Criteria:
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Are not expected to survive this PICU admission because of palliative care (e.g., do-not-resuscitate status) or limited life support
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Progressive neuromuscular disease (e.g., spinal muscular atrophy, Duchenne or other muscular dystrophy, multiple sclerosis, amyotrophic lateral sclerosis)
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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
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Contraindications to enteral nutrition (e.g., gut hemorrhage, post-gastrointestinal surgery etc.)
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Diagnosed cow's milk protein allergy
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Use of any total parenteral nutrition within first 48 hours of admission
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Premature infants who are less than corrected gestational age of 44 weeks (gestational age + weeks after birth)
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Were previously enrolled in this trial
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Are currently enrolled in a potentially confounding trial
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Diagnosis of anorexia nervosa and other eating disorders
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On extra-corporeal membrane oxygenation (ECMO) support
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Patients undergoing cardiac surgery that required significant fluid restriction (≤75%)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | National University Hospital | Singapore | Singapore | 119228 |
Sponsors and Collaborators
- KK Women's and Children's Hospital
- Duke-NUS Graduate Medical School
- Singapore Clinical Research Institute
- National Medical Research Council (NMRC), Singapore
Investigators
- Principal Investigator: Jan Hau Lee, KK Women's and Children's Hospital, SingHealth
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2020/2742