Usefulness of Protein-enriched Infant Formula in Pediatric Intensive Care.

NCT ID: NCT03901742

Last Updated: 2019-08-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

90 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-12-28

Study Completion Date

2020-12-31

Brief Summary

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A multicenter prospective randomized controlled trial (RCT) will be performed in three hospitals. Patients meeting inclusion criteria will be randomly allocated to one of three enteral feeding formula with different protein content. Blood and urine test, nitrogen balance assessment and energy expenditure testing by indirect calorimetry will be performed at the beginning of nutrition regimen and at 24 hours, 72 hours and 5-7 days after initiation. The sample size for this trial is estimated as 90 participants, with approximately 30 participants in each group. The data analysis will be by intention to treat. This RCT will provide new data about the amount of protein needed to improve levels of serum protein and nitrogen balance, surrogate of protein balance, in critically ill infants receiving enteral nutrition.

Detailed Description

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Background Protein-caloric malnutrition, with an incidence of 15-20 %, is the most important type of malnutrition in Pediatric Intensive Care Units (PICU). It is associated to poor outcomes in critically ill children: malnourished patients present an increased physiologic instability and quantity of care, with higher duration of mechanic ventilation and length of stay and increased mortality.

Current recommendations about protein prescription in critically ill children are fundamentally based on expert opinions, since studies on protein supplementation are scarce, with small sample sizes and heterogeneous patient populations, doses of protein and route of administration.

Study design Once an eligible patient is admitted to PICU, written informed consent will be requested from parents or legal representative of the child by the physician responsible of the patient. They will be made aware that participation is voluntary, and they will be allowed to refuse further participation in the trial whenever they want.

After enrolment, the patient will be allocated randomly, in order of recruitment, into one of the three 3 diet groups using a randomized data table generated with Epidat 3.1 software. A copy of the randomization list will be securely stored in an envelope located at PICU working area desk drawer, which will be opened after the patient enrolment on the study. Physicians, care givers and investigators will know the allocation prior to the start of enteral feeding.

All patients will receive exclusively enteral nutrition via nasogastric o transpyloric tube.

Since this is an open-label trial, the assigned diet will be written down on the medical prescription of each patient and will be prepared by the PICU staff at the own unit, using for it the branded bottles where the different formula are commercialized.

Continuous enteral nutrition will be initiated within the first 24 hours of PICU admission, by transpyloric or nasogastric tube, at a rate of 0.5-1 ml/kg/hour, with increases of 0.5-1 ml/kg every 3-4 hours, if well tolerated, to reach a caloric intake of 60-65 kcal/kg/day, or as needed based on resting energy expenditure measured by indirect calorimetry Demographic data will be recorded at inclusion: gender, age, weight, height, and diagnosis on admission. The risk of mortality at admission will be calculated using pediatric scales: Pediatric Index of Mortality 2 (PIM2), Pediatric Risk of Mortality (PRISM), and Pediatric Logistic Organ Dysfunction (PELOD).

Blood concentrations of urea, creatinine, total proteins, albumin, prealbumin, transferrin, retinol-binding protein (RBP) levels, urinary concentration of urea in 24-hours or isolated urine sample, and energy expenditure, oxygen consumption (VO2) and carbon dioxide production (VCO2) by indirect calorimetry (Datex S5 monitor, E-COVX; General Electrics Healthcare/Datex-Ohmeda, Helsinki, Finland) will be measured at admission and at days 1, 3 and 5-7 after initiation of enteral feeding. Air leaks will be measured using the mechanical ventilator. Calorimetry-derived data will be collected only in patients with tracheal intubation, when air leakage is \<10 %, fraction of inspired oxygen (FiO2) less than 80 %, absence of inhaled nitric oxide, sevoflurane or heliox, or connection to extracorporeal membrane oxygenation (ECMO). The collection of indirect calorimetry data will be done over 30 to 120 minutes.

Nitrogen Balance (NB) will be calculated as: nitrogen intake minus total nitrogen losses. Total nitrogen losses will include total urinary nitrogen and fecal/miscellaneous losses estimated according to the World Health Organization recommendations.

Other blood biochemical parameters as glucose, cholesterol, triglycerides, ions and blood gas will also be recorded.

Total daily enteral energy and protein delivery, intravenous albumin infused, and other treatments such as vasoactive drugs, neuromuscular blockers, sedatives and analgesic drugs, diuretics and steroids would be registered.

Protein-enriched diet safety Enteral complications (constipation, diarrhoea, abdominal distension, gastric residue), serum urea and total protein levels, as well as any unexpected adverse event occurring during the trial will be recorded to evaluate the safety of the protein-enriched diet.

Statistical analysis As there are not previous studies reporting expected standard deviations, the standardized difference of means for computing the optimal minimum number of patients to include in the trial will be used. The calculation of the sample size has been done with Epidat 3.1 software. Considering a significance level of 5% (Type I error), a power of 80% (complementary of the Type II error) and a minimum detectable standardized difference of means of 0.9, 30 patients per group are needed (Bonferroni correction included).

An intention-to-treat approach will be used. A descriptive analysis will be performed where quantitative variables will be described by their means and standard deviations or their medians and interquartile ranges, as appropriate. The quantitative ones will be summarized by their absolute and relative frequencies. Parametric and non-parametric tests will be employed for contrasting equality among groups.

Univariate and multivariate mixed models will be used in order to assess the effects size of the different diets (fixed effects) on the patients (random effects) unadjusted and adjusted by potential confounders, respectively. P-values under 5% will be considered statistically significant.

Conditions

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Protein-Energy Malnutrition

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Standard Enteral Nutrition

Standard Enteral Nutrition: cow's milk based infant formula (Nidina, Nestlé, Barcelona, Spain).

Group Type ACTIVE_COMPARATOR

Standard Enteral Nutrition

Intervention Type OTHER

Cow's milk based infant formula.

Protein-enriched nutrition

Protein-enriched Enteral Nutrition: polymeric infant formula (Infatrini; Nutricia, Madrid, Spain)

Group Type ACTIVE_COMPARATOR

Protein-enriched nutrition

Intervention Type OTHER

Protein-enriched enteral nutrition with a polymeric infant formula

High Protein-enriched Nutrition

High Protein-enriched Enteral Nutrition: polymeric infant formula (Infatrini; Nutricia, Madrid, Spain) supplemented with 2.6 g of protein/100 mL of formula. The source of the protein supplement would be a nonhydrolyzed protein cow's milk-based formula (Resource Protein Instant; Nestlé, Barcelona, Spain). Final composition 5.1 g/100 mL.

Group Type ACTIVE_COMPARATOR

High Protein-enriched Nutrition

Intervention Type DIETARY_SUPPLEMENT

High protein-enriched enteral nutrition with a polymeric infant formula plus a protein supplement

Interventions

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Protein-enriched nutrition

Protein-enriched enteral nutrition with a polymeric infant formula

Intervention Type OTHER

High Protein-enriched Nutrition

High protein-enriched enteral nutrition with a polymeric infant formula plus a protein supplement

Intervention Type DIETARY_SUPPLEMENT

Standard Enteral Nutrition

Cow's milk based infant formula.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. Children aged 1 month to 2 years.
2. Children admitted to PICU.
3. Children receiving enteral nutrition with an estimated length of over 72 hours.

Exclusion Criteria

1. Age less than 1 month or over 2 years.
2. Diabetes mellitus or any inborn metabolic error.
3. Parenteral nutrition.
4. Bicarbonate infusion.
5. Renal replacement therapy.
6. Children receiving exclusive breastfeeding or in a need of special enteral formula.
Minimum Eligible Age

1 Month

Maximum Eligible Age

2 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Maternal, Neonatal and Child Health Research Network

OTHER

Sponsor Role collaborator

European Regional Development Fund

OTHER

Sponsor Role collaborator

Instituto de Salud Carlos III

OTHER_GOV

Sponsor Role collaborator

Hospital General Universitario Gregorio Marañon

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Angel P Carrillo, PhD, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital General Universitario Gregorio Marañón. Pediatric Intensive Care Unit.

Locations

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Hospital Clínico Universitario de Santiago-CHUS

Santiago de Compostela, Galicia, Spain

Site Status RECRUITING

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, Spain

Site Status RECRUITING

Hospital General Universitario Gregorio Marañón

Madrid, , Spain

Site Status RECRUITING

Countries

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Spain

Central Contacts

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Javier Urbano, PhD, MD

Role: CONTACT

+34915290328

Jesús López-Herce, PhD, MD

Role: CONTACT

+34915290328

Facility Contacts

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Antonio Rodriguez, PhD, MD

Role: primary

+34 606796362

Corsino Rey, PhD, MD

Role: primary

+34985108000

Javier Urbano, PhD, MD

Role: primary

+34915290328

Jesús López-Herce, PhD, MD

Role: backup

+34915290328

References

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Fernandez R, Urbano J, Carrillo A, Vivanco A, Solana MJ, Rey C, Lopez-Herce J. Comparison of the effect of three different protein content enteral diets on serum levels of proteins, nitrogen balance, and energy expenditure in critically ill infants: study protocol for a randomized controlled trial. Trials. 2019 Oct 11;20(1):585. doi: 10.1186/s13063-019-3686-8.

Reference Type DERIVED
PMID: 31604481 (View on PubMed)

Other Identifiers

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FIBHGM-ECNC011-2010

Identifier Type: -

Identifier Source: org_study_id

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