Renoir: A Randomised, Double-blind, Controlled Trial to Evaluate the Effects of a New Human Milk Fortifier on Growth and Tolerance in Preterm Infants.

Study Overview
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Brief Summary
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Preterm birth (birth before start of the 37th week of gestation) is a major determinant of neonatal morbidity and mortality and has long-term adverse consequences for health and neurodevelopment. Preterm infants have much higher nutrient requirements than term infants. The preferred nutrition for all infants including preterm infants is human milk from the infant's own mother, or alternatively donor human milk, provided it is fortified with several nutrients as human milk alone does not sufficiently meet the nutritional needs of preterm infants. Human milk fortifiers (HMFs) are multicomponent enrichments that can be added to human milk (own mother´s milk or donor milk) to meet the increased nutritional needs of preterm infants. The current Nutricia HMF (control product) has been available in its current composition since 2010. It is a multicomponent HMF providing protein, energy, minerals, and vitamins in accordance with the ESPGHAN recommendations. Recent investigation suggests positive effects on growth and development of preterm infants when lipids are added to their nutrition. Therefore, Nutricia has added lipids to their HMF (test product) for a nutritionally more complete fortification of human milk aiming for optimal growth and optimal cognitive and brain development. The Renoir study will investigate the difference between both HMFs with regards to the growth velocity as well as the safety and tolerance of the new HMF.

Official Title
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Renoir: A Randomised, Double-blind, Controlled Trial to Evaluate the Effects of a New Human Milk Fortifier on Growth and Tolerance in Preterm Infants.

Conditions
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Subjects in Need of a Human Milk Fortifier (HMF), Growth, Tolerance, Safety

Intervention / Treatment
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* Other: Test product
* Other: Control product


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Preterm infants fed own mother's milk (or donor human milk) in need of a HMF (as decided by the investigator) Gestational age <32 weeks and birth weight <1500 g Receiving enteral feeding Expected to need a HMF for minimally 21 days Written informed consent from custodial parent(s) Exclusion Criteria: Any relevant proven or suspected chromosomal anomaly, metabolic disorder, genetic syndrome or congenital central nervous system malformation; Presence or history of any gastrointestinal malformation, including Necrotising enterocolitis (NEC) (defined as Bell's stage two or higher); No realistic prospect of survival at the discretion of the attending physician; Participation in any other studies involving investigational or marketed products concomitantly or within two weeks prior to entry into the study; Expected or foreseen inability of the subject and/or their families to adhere to protocol instructions.

Ages Eligible for Study
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Minimum Age: 1 Week
Maximum Age: 32 Weeks

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test product<br>Human Milk Fortifier (HMF) with added lipids. | Other: Test product<br>* HMF with added lipids - Intervention group<br>|
| Active Comparator: Control product<br>Commercially available HMF (without lipids). | Other: Control product<br>* Commercially available HMF (without lipids) - control group<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight growth velocity | Weight growth velocity (in g/kg/day) from baseline to study day 21 | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length | Length gain (cm/week) | up to 16 weeks, depending on gestational age at birth | 
| Head circumference | Head circumference gain (cm/week) | up to 16 weeks, depending on gestational age at birth | 
| Weight for Length | Weight for Length | up to 16 weeks, depending on gestational age at birth | 
| Z-scores | Z-scores (no unit) of anthropometric measures (weight for age, length for age, head circumference for age) | up to 16 weeks, depending on gestational age at birth | 
| Stool consistency | Stool consistency (4-point scale Amsterdam stool scale: watery, soft, formed, hard) | up to 16 weeks, depending on gestational age at birth | 
| Stool frequency | Stool frequency (number of stools per day) | up to 16 weeks, depending on gestational age at birth | 
| Enteral intake | Total enteral intake (mL/kg/day) | up to 16 weeks, depending on gestational age at birth | 
| vomiting | Incidence of vomiting (number/day) | up to 16 weeks, depending on gestational age at birth | 
| Regurgitation | Incidence of regurgitation (number/day) | up to 16 weeks, depending on gestational age at birth | 
| Enteral feed | Number of days that an infant is not fed enterally | up to 16 weeks, depending on gestational age at birth. |