Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT03775785 |
| Other study ID # |
1/2018 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
July 1, 2019 |
| Est. completion date |
December 31, 2024 |
Study information
| Verified date |
December 2021 |
| Source |
Princess Anna Mazowiecka Hospital, Warsaw, Poland |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
BACKGROUND:
Human milk (HM) is recommended for all very low birth infants (VLBW)). Breast-milk is highly
variable in nutrient content, failing to meet the nutritional demands of VLBW. Fortification
of HM is recommended to prevent extra-uterine growth retardation and associated poor
neurodevelopmental outcome. However, standard fortification with fixed dose multicomponent
fortifier does not account for the variability in milk composition. Targeted fortification is
a promising alternative and needs further investigation.
The aim of the study is to evaluate if targeted fortification of human milk may optimize
growth and development in preterm infants.
STUDY DESIGN:
Randomized single blind controlled trial.
METHODS & ANALYSIS:
We will recruit preterm infants (≤ 32 weeks of gestation) within the first 7 days of life.
After reaching 80 ml/kg/day of enteral feeding, patients will be randomised to receive
standard fortification (HMF, Nutricia) or targeted fortification (modular components: Bebilon
Bialko, Nutricia - protein, Fantomalt, Nutricia - carbohydrates, Calogen, Nutricia - lipids).
The intervention will continue until 37 weeks of post-conception age, or hospital discharge.
Parents and outcome assessors will be blinded to the intervention.
The primary outcome - weight gain velocity will be measured starting from the day infants
regain their birth weight up to 4 weeks, then weekly until discharge.
Secondary outcomes such as neurodevelopment at 12 months of corrected age (CA) will be
assessed with Bayley Scale of Development III, repeated at 36 months of CA. Additionally a
Wescheler Preschool and Primary Scale of Intelligence IV test will be applied at 3,5 years of
CA. Secondary outcomes such as length and head growth, body composition will be assesed at
discharge and at 4 months. Incidence of necrotizing enterocolitis (NEC), sepsis, retinopathy
of prematurity (ROP) and bronchopulmonary dysplasia (BPD) will also be followed.
Description:
Study design and setting This is a multi-centre superiority randomised parallel group, 1:1
allocation study. Patients will be recruited at three departments of neonatology and
intensive care units: Department of Neonatology and Neonatal Intensive Care, Division of
Neonatal Intensive Care (Medical University of Warsaw), and the Institute of Mother and
Child. Follow up will be carried out at the Department of Paediatrics.
The study is lead by the Department of Neonatology and Neonatal Intensive Care (KAROWA) with
approximately 3000 (100 ≤ 32 weeks of gestation) deliveries per year and 12 intensive care
and 40 high dependency neonatal beds.
Recruitment Recruitment will take place between June 2019 and December 2020. Parents of
infants born at less than 32 weeks of gestation will be approached within the first week of
life.
Randomisation After reaching 80 ml/kg/day of enteral feeding, patients will be randomised to
receive standard fortification (SF) or targeted fortification (TF) (proteins, lipids,
carbohydrates). Allocation will be performed electronically.
Interventions Human milk fortification procedure Milk fortification will be done twice a day
(8 am and 8 pm) for each following 12 hour nursing shift (Appendix 1).
A 10 mL aliquot from each batch of native breast milk will be used for macronutrient analysis
using a human milk analyser Miris® as per protocol. The remaining batch will first be
fortified with the standard fortifier. Macronutrient analysis will determine how much extra
fat, protein, and/or carbohydrate is needed to obtain target fortified breast milk.
An experienced laboratory technician will perform milk analysis in the neonatal intensive
care unit (NICU) research laboratory at KAROWA twice per week at 10:00 am (Monday/Friday)
from batches collected from the two previous days. Milk samples from other sites will be
delivered by medical transport in secure freezing containers at 8:00 am.
The mean of three measurements per batch (3 x 2-3ml) will be used to calculate the required
amount of extra fat, protein, and carbohydrate for the following 3 days of fortification
using a predefined Excel spread sheet (Microsoft Inc, Redmond, Washington). Milk analysis
will be performed in both treatment arms; however only the intervention group will receive
TF. Results, together with required amounts of macronutrients, will be emailed to the
participating centres before noon the same day.
The defined macronutrient concentration in breast milk is 4.4 g/100 mL of fat, 3 g/100 mL of
protein, and 8.8 g/ 100 mL of carbohydrate to meet the European Society for Paediatric
Gastroenterology, Hepatology, and Nutrition (ESPGHAN) guidelines (6.6 g/kg/d of fat, 4.5
g/kg/d of protein, and 13.2 g/kg/d of carbohydrate) assuming an intake of 150 mL/kg/d.
Target fortification will be done in 3 steps:
1. Determination of macronutrients concentration in own mothers´s milk (OMM)/human donor
milk (HDM).
2. Standard fortification (SF) (human milk fortifier - HMF).
3. Targeted fortification (TF): adding fat, protein, and/or carbohydrate to achieve target
levels of macronutrients.
In cases where a macronutrient component after SF will exceed the target value, only the
other deficient macronutrient components will be adjusted.
Safety Prescription of TF will be completed before noon. Bedside nurses will prepare batches
of fortified breast milk including the additives for TF.
Data from breast milk analyses, fortification, and enteral intake will be documented daily.
Acid base status, blood urea nitrogen (BUN), and glucose will be determined as per NICU
routine.
The intervention will continue until 37 weeks of post-conception age, or hospital discharge.
Parents and outcome assessors will be blinded to the intervention.
Randomization A study number together with the allocated treatment will be assigned by the
platform. Patient's data along with the result of the allocation will be sent to statistical
team. The randomisation list will remain with the statistical team for the whole duration of
the study. Randomisation will be conducted without any influence of the principal
investigators, clinicians, recruitment or follow up staff.
Blinding The decision to start fortification will be made by the attending physician blinded
to the intervention allocated. An employee outside the research team will feed data into the
computer in separate datasets so that the researchers can analyse data without having access
to information about the allocation.
Sample size The sample size required to compare two means in two-sided equality test was
estimated based on results from a prior double blind, randomised clinical trial,
investigating the effect of target fortification vs standard fortification of breast milk on
the changes of anthropometric parameters and body composition in preterm children. It was
determined, that a mean difference of weight gain 1.9 g/kg/day between groups would be
clinically important and feasible during intervention. between the study groups with a power
of 80% and α=0.05, a sample of 91 infants is needed in each study group. Allowing for 10% of
loss to follow-up, the target number of 200 premature infants will be recruited.
