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

Safety Clinical Trial

— Renoir  

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.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03315221
• Other study ID #: EBB16GL06402
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: March 8, 2018
• Est. completion date: June 2022

Study information

• Verified date: December 2021
• Source: Nutricia Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 182
• Est. completion date: June 2022
• Est. primary completion date: June 26, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 32 Weeks

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Other:
• Test product
HMF with added lipids - Intervention group
• Control product
Commercially available HMF (without lipids) - control group

Locations

Country	Name	City	State
France	Hôpital de la Croix Rousse	Lyon
France	CHRU Nancy - Maternité regionale Universitaire A. Pinard	Nancy
Germany	Universitätskinderklinik der Otto-v.-Guericke Universität	Magdeburg
Germany	Klinikum Nürnberg Süd	Nürnberg
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
United Kingdom	Saint-Peter's Hospital NHS Foundation Trust	Chertsey
United Kingdom	Norfolk and Norwich NHS Foundation Trust	Norwich

Sponsors (1)

Lead Sponsor	Collaborator
Nutricia Research

Countries where clinical trial is conducted

France,  Germany,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory - Age	Age at discharge from the neonatal intensive care unit (NICU, level III)	2-16 weeks, depending on gestational age at birth
Other	Exploratory - Age	Age at discharge home	4-16 weeks depending on gestational age at birth
Other	Exploratory - Mortality	Mortality (yes/no) during stay in NICU/hospital	up to 16 weeks depending on gestational age at birth
Other	Exploratory - Enteral feeding volume	Time in days to achieve an enteral feeding volume of at least 150 mL/kg/day +/- 10 mL for 3 consecutive days	around 1-4 weeks, depending on gestational age at birth
Other	Exploratory - Gastric residuals	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)	up to 16 weeks, depending on gestational age at birth
Other	Exploratory - Diarrhoea	Occurrence of diarrhoea	up to 16 weeks, depending on gestational age at birth)
Other	Exploratory - Constipation	Occurrence of constipation	up to 16 weeks, depending on gestational age at birth)
Other	Exploratory - Weight	Weight (g)	at 6, 12 and 24 months corrected age (CA)
Other	Exploratory - Length	Length (cm)	at 6, 12 and 24 months corrected age (CA)
Other	Exploratory - Head circumference	Head circumference (cm)	at 6, 12 and 24 months corrected age (CA)
Other	Exploratory - Neurodevelopmental outcome	Neurodevelopmental outcome assessed by Bayley Scales of Infant and Toddler Development, Third Edition, on three subscales (cognitive, fine and gross motor)	at 24 months CA
Other	Safety - Incidence (S)AE's	Incidence of (Serious) Adverse Events that are assessed by the Investigator to be possibly, probably or definitely related to the study product	up to 24 months CA
Other	Safety - Frequency (S)AE's	Frequency of (Serious) Adverse Events that are assessed by the Investigator to be possibly, probably or definitely related to the study product	up to 24 months CA
Other	Safety - Severity (S)AE's	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	up to 24 months CA
Other	Safety - Relatedness (S)AE's	Relatedness of Serious Adverse Events	up to 24 months CA
Other	Safety - Incidence Blood in stool	Incidence blood in stool	up to 16 weeks, depending on gestational age at birth)
Other	Safety - Frequency Blood in stool	Frequency of blood in stool	up to 16 weeks, depending on gestational age at birth)
Other	Safety - Severity Blood in stool	Severity of blood in stool (mild, moderate, severe)	up to 16 weeks, depending on gestational age at birth)
Other	Safety - NEC	NEC (defined as Bell's stage two or higher) (as part of the assessment of neonatal morbidity)	up to 16 weeks, depending on gestational age at birth)
Other	Safety - Bronchopulmonary dysplasia	Bronchopulmonary dysplasia (as part of the assessment of neonatal morbidity), categorized into mild/moderate/severe based on Sahni et al	up to 16 weeks, depending on gestational age at birth)
Other	Safety - Serious neonatal infections	Serious neonatal infections (as part of the assessment of neonatal morbidity), i.e. confirmed sepsis, pneumonia, or meningitis	up to 16 weeks, depending on gestational age at birth
Other	Safety - Retinopathy of Prematurity	Retinopathy of Prematurity, based on International Committee for the Classification of Retinopathy of Prematurity (as part of the assessment of neonatal morbidity)	up to 16 weeks, depending on gestational age at birth
Other	Safety - Metabolic acidosis	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)	up to 16 weeks, depending on gestational age at birth
Primary	Weight growth velocity	Weight growth velocity (in g/kg/day) from baseline to study day 21	21 days
Secondary	Length	Length gain (cm/week)	up to 16 weeks, depending on gestational age at birth
Secondary	Head circumference	Head circumference gain (cm/week)	up to 16 weeks, depending on gestational age at birth
Secondary	Weight for Length	Weight for Length	up to 16 weeks, depending on gestational age at birth
Secondary	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
Secondary	Stool consistency	Stool consistency (4-point scale Amsterdam stool scale: watery, soft, formed, hard)	up to 16 weeks, depending on gestational age at birth
Secondary	Stool frequency	Stool frequency (number of stools per day)	up to 16 weeks, depending on gestational age at birth
Secondary	Enteral intake	Total enteral intake (mL/kg/day)	up to 16 weeks, depending on gestational age at birth
Secondary	vomiting	Incidence of vomiting (number/day)	up to 16 weeks, depending on gestational age at birth
Secondary	Regurgitation	Incidence of regurgitation (number/day)	up to 16 weeks, depending on gestational age at birth
Secondary	Enteral feed	Number of days that an infant is not fed enterally	up to 16 weeks, depending on gestational age at birth.