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

Primary Purpose

Protein-Energy Malnutrition

Status
Unknown status
Phase
Not Applicable
Locations
Spain
Study Type
Interventional
Intervention
Protein-enriched nutrition
High Protein-enriched Nutrition
Standard Enteral Nutrition
Sponsored by
Hospital General Universitario Gregorio Marañon
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Protein-Energy Malnutrition focused on measuring Children, Intensive Care, Nutrition, Enteral feeding, Protein intake, Protein balance., Lean Body Mass

Eligibility Criteria

1 Month - 2 Years (Child)All SexesDoes not accept healthy volunteers

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: Children who met any of the following criteria will be excluded:

  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.

Sites / Locations

  • Hospital Universitario Central de AsturiasRecruiting
  • Hospital Clínico Universitario de Santiago-CHUSRecruiting
  • Hospital General Universitario Gregorio MarañónRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Active Comparator

Arm Label

Standard Enteral Nutrition

Protein-enriched nutrition

High Protein-enriched Nutrition

Arm Description

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

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

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.

Outcomes

Primary Outcome Measures

Nitrogen balance variation
The variation of nitrogen balance (NB) from baseline to the study ending
Proportion of patients that meet study ending criteria
Study ending criteria: serum urea levels elevates higher than 80 mg/dL without evidence of renal function disturbance or hypercatabolism; hyperproteinemia higher than 8.5 g/dL .

Secondary Outcome Measures

variation of plasma protein levels
variation of plasma protein levels (mg/dL) (total proteins, albumin, prealbumin, transferrin and retinol-binding protein)
variation of resting energy expenditure
variation of resting energy expenditure measured with indirect calorimetry during the study period.
the incidence of gastrointestinal complications
Gastrointestinal complications: abdominal distension, vomiting, diarrhea and excessive gastric residue

Full Information

First Posted
March 25, 2019
Last Updated
August 21, 2019
Sponsor
Hospital General Universitario Gregorio Marañon
Collaborators
Maternal, Neonatal and Child Health Research Network, European Regional Development Fund, Instituto de Salud Carlos III
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1. Study Identification

Unique Protocol Identification Number
NCT03901742
Brief Title
Usefulness of Protein-enriched Infant Formula in Pediatric Intensive Care.
Official Title
Effect of the Administration of an Enteral Milk Supplemented With Proteins to Infants Admitted in a Pediatric Intensive Care Unit
Study Type
Interventional

2. Study Status

Record Verification Date
August 2019
Overall Recruitment Status
Unknown status
Study Start Date
December 28, 2016 (Actual)
Primary Completion Date
December 2020 (Anticipated)
Study Completion Date
December 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospital General Universitario Gregorio Marañon
Collaborators
Maternal, Neonatal and Child Health Research Network, European Regional Development Fund, Instituto de Salud Carlos III

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Protein-Energy Malnutrition
Keywords
Children, Intensive Care, Nutrition, Enteral feeding, Protein intake, Protein balance., Lean Body Mass

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Standard Enteral Nutrition
Arm Type
Active Comparator
Arm Description
Standard Enteral Nutrition: cow's milk based infant formula (Nidina, Nestlé, Barcelona, Spain).
Arm Title
Protein-enriched nutrition
Arm Type
Active Comparator
Arm Description
Protein-enriched Enteral Nutrition: polymeric infant formula (Infatrini; Nutricia, Madrid, Spain)
Arm Title
High Protein-enriched Nutrition
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
Protein-enriched nutrition
Intervention Description
Protein-enriched enteral nutrition with a polymeric infant formula
Intervention Type
Dietary Supplement
Intervention Name(s)
High Protein-enriched Nutrition
Intervention Description
High protein-enriched enteral nutrition with a polymeric infant formula plus a protein supplement
Intervention Type
Other
Intervention Name(s)
Standard Enteral Nutrition
Intervention Description
Cow's milk based infant formula.
Primary Outcome Measure Information:
Title
Nitrogen balance variation
Description
The variation of nitrogen balance (NB) from baseline to the study ending
Time Frame
From date of randomization until the date of first documented progression or date of discharge, whichever came first, assessed up to 7 days
Title
Proportion of patients that meet study ending criteria
Description
Study ending criteria: serum urea levels elevates higher than 80 mg/dL without evidence of renal function disturbance or hypercatabolism; hyperproteinemia higher than 8.5 g/dL .
Time Frame
From date of randomization until the date of first documented progression or date of discharge, whichever came first, assessed up to 7 days
Secondary Outcome Measure Information:
Title
variation of plasma protein levels
Description
variation of plasma protein levels (mg/dL) (total proteins, albumin, prealbumin, transferrin and retinol-binding protein)
Time Frame
From date of randomization until the date of first documented progression or date of discharge, whichever came first, assessed up to 7 days
Title
variation of resting energy expenditure
Description
variation of resting energy expenditure measured with indirect calorimetry during the study period.
Time Frame
From date of randomization until the date of first documented progression or date of discharge, whichever came first, assessed up to 7 days
Title
the incidence of gastrointestinal complications
Description
Gastrointestinal complications: abdominal distension, vomiting, diarrhea and excessive gastric residue
Time Frame
From date of randomization until the date of first documented progression or date of discharge, whichever came first, assessed up to 7 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Month
Maximum Age & Unit of Time
2 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Children aged 1 month to 2 years. Children admitted to PICU. Children receiving enteral nutrition with an estimated length of over 72 hours. Exclusion Criteria: Children who met any of the following criteria will be excluded: Age less than 1 month or over 2 years. Diabetes mellitus or any inborn metabolic error. Parenteral nutrition. Bicarbonate infusion. Renal replacement therapy. Children receiving exclusive breastfeeding or in a need of special enteral formula.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Javier Urbano, PhD, MD
Phone
+34915290328
Email
javierurbanovillaescusa@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Jesús López-Herce, PhD, MD
Phone
+34915290328
Email
pielvi@hotmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Angel P Carrillo, PhD, MD
Organizational Affiliation
Hospital General Universitario Gregorio Marañón. Pediatric Intensive Care Unit.
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital Universitario Central de Asturias
City
Oviedo
State/Province
Asturias
ZIP/Postal Code
33011
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Corsino Rey, PhD, MD
Phone
+34985108000
Email
crey@uniovi.es
First Name & Middle Initial & Last Name & Degree
Reyes Fernández, MD
First Name & Middle Initial & Last Name & Degree
Corsino Rey, PhD, MD
Facility Name
Hospital Clínico Universitario de Santiago-CHUS
City
Santiago De Compostela
State/Province
Galicia
ZIP/Postal Code
15706
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antonio Rodriguez, PhD, MD
Phone
+34 606796362
Email
Antonio.Rodriguez.Nunez@sergas.es
First Name & Middle Initial & Last Name & Degree
Antonio Rodriguez, PhD, MD
Facility Name
Hospital General Universitario Gregorio Marañón
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Javier Urbano, PhD, MD
Phone
+34915290328
Email
javierurbanovillaescusa@gmail.com
First Name & Middle Initial & Last Name & Degree
Jesús López-Herce, PhD, MD
Phone
+34915290328
Email
pielvi@hotmail.com
First Name & Middle Initial & Last Name & Degree
Angel P Carrillo, PhD, MD
First Name & Middle Initial & Last Name & Degree
Jesus López-Herce, PhD, MD
First Name & Middle Initial & Last Name & Degree
Javier Urbano, PhD, MD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
All collected individual participant data (IPD)
IPD Sharing Time Frame
At the end of the study
Citations:
PubMed Identifier
31604481
Citation
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.
Results Reference
derived

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

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