The Effect of High-Calorie Formula on Nutritional and Clinical Outcomes Among Infants After Congenital Heart Surgery

Study Overview
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Brief Summary
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The goal of this clinical trial is to compare the effect of high-calorie density formula (HDF) and standard formula (SF) in infants with congenital heart surgery. The main questions it aims to answer are: Is there any difference in nutritional status between both groups after 3 months? Is there any difference in calorie intake per day between both groups during hospitalization? Is there any difference in clinical outcomes (mortality, duration of using mechanical ventilation, length of stay, and events of side effects) between both groups? A group of participants will be given HDF (1 kcal/ml) from enrollment until three months. Researchers will compare them to the group of participants who are given SF (0.67 kcal/ml) to see if there is any difference in nutritional status, calorie intake, and other clinical outcomes between the two groups.

Detailed Description
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The study is a randomized, double-blind controlled trial to compare the efficacy of HDF formula compared to SF in nutritional and clinical outcomes among infants who had congenital heart surgery in Harapan Kita National Cardiovascular Centre (HKNCC), Jakarta, Indonesia. The researchers use consecutive sampling to include eligible infants and obtain informed consent from the parent or legal guardian of infants who fulfilled the eligibility criteria. Block randomization is done by a research assistant, and then the allocation is prepared using a sealed envelope to assign infants into HDF and SF groups. Participants are then assessed by a multi-professional team and given enteral feeds based on local guidelines. Routine follow-up is done at 2 weeks, 1 month, 2 months, and 3 months after the intervention to record weight, length, and any episode of complication or adverse events.

Official Title
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The Effect of High-calorie Density Formula Versus Standard Formula in Calorie Intake, Nutritional Status, and Clinical Outcomes Among Infants Who Underwent Congenital Heart Disease Surgery: A Randomized, Double-blind Controlled Trial

Conditions
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Congenital Heart Disease in Children, Malnutrition, Child

Intervention / Treatment
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* Dietary Supplement: High-calorie density formula (1 kcal/ml)
* Dietary Supplement: Standard formula (0.67 kcal/ml)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient of less than 1 year of age who underwent congenital heart surgery procedure in Harapan Kita National Cardiovascular Center Risk adjustment for congenital heart surgery (RACHS) score 2-4 Patients who do not get exclusive breastfeeding due to any cause Exclusion Criteria: History of prematurity (<37 weeks gestational age) Formula intolerance or cow milk protein allergy Lethal chromosome abnormality Galactosemia Gastrointestinal malformation or obstruction Renal failure Liver disease Metabolic abnormalities Need for extracorporeal membrane oxygenation Drop-out Patients who develop diarrhea for more than 5 days during the study period despite getting adequate therapy Patients who need prolonged total parenteral nutrition (e.g., gastrointestinal bleeding due to any cause, chylothorax, etc.) Patients with necrotizing enterocolitis during the study period

Ages Eligible for Study
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Minimum Age: 14 Days
Maximum Age: 1 Year

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention arm<br>High-calorie density formula (1 kcal/ml) | Dietary Supplement: High-calorie density formula (1 kcal/ml)<br>* The dose is started from 20ml/kg/day divided into 8 feeds and increased by 20ml/kg/day until the feeding goal is reached (120-150ml/kg/day) during hospitalization. The intervention is then continued after discharge for 3 months (ad libitum).<br>|
| Placebo Comparator: Control arm<br>Standard formula (0.67 kcal/ml) | Dietary Supplement: Standard formula (0.67 kcal/ml)<br>* The dose is started from 20ml/kg/day divided into 8 feeds and increased by 20ml/kg/day until the feeding goal is reached (120-150ml/kg/day) during hospitalization. The intervention is then continued after discharge for 3 months (ad libitum).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nutritional status | Numeric data of weight-for-length z-score (WLZ), length-for-age z-score (LAZ) and weight-for-age z-score (WAZ) based on the 2006 World Health Organization (WHO) Child Growth Standard | After 3 months of intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Calorie intake | Numeric data of the infants' total calorie intake (kcal/kg/day) during hospitalization | From the date of randomization to the date of discharge, assessed up to 3 months | 
| Weight | Numeric data of absolute weight (kg) | After 1, 2, and 3 months of intervention | 
| Length | Numeric data of absolute length (cm) | After 1, 2, and 3 months of intervention | 
| Weight-for-age z-score changes | Difference of weight-for-age z-score based on The 2006 WHO Child Growth Standard | From the date of randomization to after 1, 2, and 3 months of intervention | 
| Length-for-age z-score changes | Difference of length-for-age z-score based on The 2006 WHO Child Growth Standard | From the date of randomization to after 1, 2, and 3 months of intervention | 
| Weight-for-length z-score changes | Difference of weight-for-length z-score based on The 2006 WHO Child Growth Standard | From the date of randomization to after 1, 2, and 3 months of intervention | 
| Malnutrition risk | Risk ratios of malnutrition, defined as weight-for-length <-2 based on 2006 WHO Child Growth Standard | After 1, 2, and 3 months of intervention | 
| Mortality | The event proportion of mortality (%) | Through study completion, an average of 3 months | 
| Duration of mechanical ventilation | The difference of mechanical ventilation duration (hours) | From the date of randomization to the date of hospital discharge, assessed up to 3 months | 
| Length of stay | The difference of lengths of stay in intensive care unit and hospital (days) | From the date of randomization to the date of discharge, assessed up to 3 months | 
| Side effects | The event proportion (%) of vomiting, diarrhea, gastrointestinal bleeding, constipation, and >50% residual gastric content | From the date of randomization to the date of hospital discharge, assessed up to 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anthropometry, congenital heart disease, infant formula, nutritional status, randomized controlled trial