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

Critically Ill Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04565613
• Other study ID #: 2020/2742
• Status: Recruiting
• Phase: N/A
• Start date: January 25, 2021
• Est. completion date: March 2025

Study information

• Verified date: March 2024
• Source: KK Women's and Children's Hospital
• Contact: Jan Hau Lee
• Phone: 63926347
• Email: lee.jan.hau[@]singhealth.com.sg
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: March 2025
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 28 Days to 18 Years

Eligibility

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.)

Related Conditions & MeSH terms

• Critical Illness
• Critically Ill
• Thinness

Intervention

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.

Locations

Country	Name	City	State
Singapore	National University Hospital	Singapore

Sponsors (4)

Lead Sponsor	Collaborator
KK Women's and Children's Hospital	Duke-NUS Graduate Medical School, National Medical Research Council (NMRC), Singapore, Singapore Clinical Research Institute

Country where clinical trial is conducted

Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of eligible patients approached for consent	Number of eligible patients who are approached for consent	Throughout study period, over 36 months
Primary	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
Primary	Participant accrual rate	Average monthly enrolment at each centre	Throughout the study, over 24 months
Primary	Protocol adherence	>80% of protein target administered according to the protocol in the intervention arm	Throughout study period, over 24 months
Secondary	PICU mortality	Death in PICU	Throughout study period, over 36 months
Secondary	PICU length of stay	Duration of stay in the PICU	Throughout study period, over 36 months
Secondary	Hospital length of stay	Duration of stay in the hospital	Throughout the study period, over 36 months
Secondary	Adverse events	Development of adverse events such as feeding intolerance, diarrhoea, gastrointestinal bleeding	Throughout study period, over 36 months
Secondary	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
Secondary	Anthropometry	Change in anthropometric measurements	During PICU stay, PICU discharge, hospital discharge and 6 months follow-up
Secondary	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