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

• ClinicalTrials.gov Identifier: NCT03315221
• Recruitment Status: Active, not recruiting
• First Posted: October 20, 2017
• Last Update Posted: December 8, 2021
• Sponsor: Nutricia Research
• Information provided by (Responsible Party): Nutricia Research

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Subjects in Need of a Human Milk Fortifier (HMF); Growth; Tolerance; Safety	Other: Test product; Other: Control product	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 182 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Renoir: A Randomised, Double-blind, Controlled Trial to Evaluate the Effects of a New Human Milk Fortifier on Growth and Tolerance in Preterm Infants.
• Actual Study Start Date: March 8, 2018
• Actual Primary Completion Date: June 26, 2020
• Estimated Study Completion Date: June 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Test product; Human Milk Fortifier (HMF) with added lipids.	Other: Test product; HMF with added lipids - Intervention group
Active Comparator: Control product; Commercially available HMF (without lipids).	Other: Control product; Commercially available HMF (without lipids) - control group

Outcome Measures

Primary Outcome Measures :

1. Weight growth velocity [ Time Frame: 21 days ]
   Weight growth velocity (in g/kg/day) from baseline to study day 21

Secondary Outcome Measures :

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

Other Outcome Measures:

1. Exploratory - Age [ Time Frame: 2-16 weeks, depending on gestational age at birth ]
   Age at discharge from the neonatal intensive care unit (NICU, level III)
2. Exploratory - Age [ Time Frame: 4-16 weeks depending on gestational age at birth ]
   Age at discharge home
3. Exploratory - Mortality [ Time Frame: up to 16 weeks depending on gestational age at birth ]
   Mortality (yes/no) during stay in NICU/hospital
4. Exploratory - Enteral feeding volume [ Time Frame: around 1-4 weeks, depending on gestational age at birth ]
   Time in days to achieve an enteral feeding volume of at least 150 mL/kg/day +/- 10 mL for 3 consecutive days
5. Exploratory - Gastric residuals [ Time Frame: up to 16 weeks, depending on gestational age at birth ]
   Frequency of clinically significant gastric residuals, defined as gastric residuals leading to a change in feeding according to the investigator's assessment (if assessed per local standard practice)
6. Exploratory - Diarrhoea [ Time Frame: up to 16 weeks, depending on gestational age at birth) ]
   Occurrence of diarrhoea
7. Exploratory - Constipation [ Time Frame: up to 16 weeks, depending on gestational age at birth) ]
   Occurrence of constipation
8. Exploratory - Weight [ Time Frame: at 6, 12 and 24 months corrected age (CA) ]
   Weight (g)
9. Exploratory - Length [ Time Frame: at 6, 12 and 24 months corrected age (CA) ]
   Length (cm)
10. Exploratory - Head circumference [ Time Frame: at 6, 12 and 24 months corrected age (CA) ]
    Head circumference (cm)
11. Exploratory - Neurodevelopmental outcome [ Time Frame: at 24 months CA ]
    Neurodevelopmental outcome assessed by Bayley Scales of Infant and Toddler Development, Third Edition, on three subscales (cognitive, fine and gross motor)
12. Safety - Incidence (S)AE's [ Time Frame: up to 24 months CA ]
    Incidence of (Serious) Adverse Events that are assessed by the Investigator to be possibly, probably or definitely related to the study product
13. Safety - Frequency (S)AE's [ Time Frame: up to 24 months CA ]
    Frequency of (Serious) Adverse Events that are assessed by the Investigator to be possibly, probably or definitely related to the study product
14. Safety - Severity (S)AE's [ Time Frame: up to 24 months CA ]
    Severity of (Serious) Adverse Events (mild/moderate/severe) that are assessed by the Investigator to be possibly, probably or definitely related to the study product
15. Safety - Relatedness (S)AE's [ Time Frame: up to 24 months CA ]
    Relatedness of Serious Adverse Events
16. Safety - Incidence Blood in stool [ Time Frame: up to 16 weeks, depending on gestational age at birth) ]
    Incidence blood in stool
17. Safety - Frequency Blood in stool [ Time Frame: up to 16 weeks, depending on gestational age at birth) ]
    Frequency of blood in stool
18. Safety - Severity Blood in stool [ Time Frame: up to 16 weeks, depending on gestational age at birth) ]
    Severity of blood in stool (mild, moderate, severe)
19. Safety - NEC [ Time Frame: up to 16 weeks, depending on gestational age at birth) ]
    NEC (defined as Bell's stage two or higher) (as part of the assessment of neonatal morbidity)
20. Safety - Bronchopulmonary dysplasia [ Time Frame: up to 16 weeks, depending on gestational age at birth) ]
    Bronchopulmonary dysplasia (as part of the assessment of neonatal morbidity), categorized into mild/moderate/severe based on Sahni et al
21. Safety - Serious neonatal infections [ Time Frame: up to 16 weeks, depending on gestational age at birth ]
    Serious neonatal infections (as part of the assessment of neonatal morbidity), i.e. confirmed sepsis, pneumonia, or meningitis
22. Safety - Retinopathy of Prematurity [ Time Frame: up to 16 weeks, depending on gestational age at birth ]
    Retinopathy of Prematurity, based on International Committee for the Classification of Retinopathy of Prematurity (as part of the assessment of neonatal morbidity)
23. Safety - Metabolic acidosis [ Time Frame: up to 16 weeks, depending on gestational age at birth ]
    Metabolic acidosis (as part of the assessment of neonatal morbidity) leading to correction and/or change in clinical management of the subject (according to the investigator's assessment)

Eligibility Criteria

• Ages Eligible for Study: 1 Week to 32 Weeks (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Preterm infants fed own mother's milk (or donor human milk) in need of a HMF (as decided by the investigator)
2. Gestational age <32 weeks and birth weight <1500 g
3. Receiving enteral feeding
4. Expected to need a HMF for minimally 21 days
5. Written informed consent from custodial parent(s)

Exclusion Criteria:

1. Any relevant proven or suspected chromosomal anomaly, metabolic disorder, genetic syndrome or congenital central nervous system malformation;
2. Presence or history of any gastrointestinal malformation, including Necrotising enterocolitis (NEC) (defined as Bell's stage two or higher);
3. No realistic prospect of survival at the discretion of the attending physician;
4. Participation in any other studies involving investigational or marketed products concomitantly or within two weeks prior to entry into the study;
5. Expected or foreseen inability of the subject and/or their families to adhere to protocol instructions.

Contacts and Locations

Locations

France

Hôpital de la Croix Rousse

Lyon, France

CHRU Nancy - Maternité regionale Universitaire A. Pinard

Nancy, France

Germany

Universitätskinderklinik der Otto-v.-Guericke Universität

Magdeburg, Germany

Klinikum Nürnberg Süd

Nürnberg, Germany

Netherlands

Noordwest Ziekenhuisgroep

Alkmaar, Netherlands

Ziekenhuisgroep Twente

Almelo, Netherlands

Flevoziekenhuis

Almere, Netherlands

Amsterdam UMC (VUMC)

Amsterdam, Netherlands

OLVG Onze Lieve Vrouwe Gasthuis

Amsterdam, Netherlands

Spaarne Ziekenhuis

Hoofddorp, Netherlands

Maastricht UMC

Maastricht, Netherlands

VieCuri Medisch Centrum

Venlo, Netherlands

Isala Ziekenhuis

Zwolle, Netherlands

United Kingdom

Saint-Peter's Hospital NHS Foundation Trust

Chertsey, United Kingdom

Norfolk and Norwich NHS Foundation Trust

Norwich, United Kingdom

Sponsors and Collaborators

Nutricia Research

More Information

• Responsible Party: Nutricia Research
• ClinicalTrials.gov Identifier: NCT03315221
• Other Study ID Numbers: EBB16GL06402
• First Posted: October 20, 2017
• Last Update Posted: December 8, 2021
• Last Verified: December 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No