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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03822104
Other study ID # FortiColos-CN
Secondary ID
Status Completed
Phase N/A
First received
Last updated
Start date May 1, 2019
Est. completion date July 8, 2021

Study information

Verified date January 2022
Source Rigshospitalet, Denmark
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Very preterm infants (<32 weeks gestation) show the immaturity of organs and have high nutrient requirements for growth and development. In the first weeks, they have difficulties tolerating enteral nutrition (EN) and are often given supplemental parenteral nutrition (PN). A fast transition to full EN is important to improve gut maturation and reduce the high risk of late-onset sepsis (LOS), related to their immature immunity in gut and blood. Conversely, too fast increase of EN predisposes to feeding intolerance and necrotizing enterocolitis (NEC). Further, human milk feeding is not sufficient to support nutrient requirements for growth of very preterm infants. Thus, it remains a difficult task to optimize EN transition, achieve adequate nutrient intake and growth, and minimize NEC and LOS in the postnatal period of very preterm infants. Mother´s own milk (MM) is considered the best source of EN for very preterm infants and pasteurized human donor milk (DM) is the second choice if MM is absent or not sufficient. The recommended protein intake is 4-4.5 g/kg/d for very low birth infants when the target is a postnatal growth similar to intrauterine growth rates. This amount of protein cannot be met by feeding only MM or DM. Thus, it is common practice to enrich human milk with human milk fortifiers (HMFs, based on ingredients used in infant formulas) to increase growth, bone mineralization and neurodevelopment, starting from 7-14 d after birth and 80-160 ml/kg feeding volume per day. Bovine colostrum (BC) is the first milk from cows after parturition and is rich in protein (80-150 g/L) and bioactive components. These components may improve gut maturation, NEC protection, and nutrient assimilation, even across species. Studies in preterm pigs show that feeding BC alone, or DM fortified with BC, improves growth, gut maturation, and NEC resistance during the first 1-2 weeks, relative to DM, or DM fortified with conventional HMFs. On this background, the investigators hypothesize that BC, used as a fortifier for MM or DM, can reduce feeding intolerance than conventional fortifiers.


Description:

Objectives 1. To test if fortification of human milk with BC reduces feeding intolerance compared with currently used HMF. 2. To verify the safety and tolerability of BC fortification and to monitor the rates of growth, NEC and sepsis, as investigated in a parallel trial in Denmark Trial design This study is a dual-center, non-blinded, two-armed, randomized, controlled trial. Participants Parents to eligible very preterm infants admitted to the Neonatal Intensive Care Units (NICU) at Nanshan People's Hospital (NAN) and Baoan Maternal and Children's Hospital in Shenzhen, China will be asked for participation. Sample size 68 infants per group, 136 in total Data type Clinical data A parallel trial on BC used as human milk fortifier is conducting in Denmark (NCT03537365)


Recruitment information / eligibility

Status Completed
Enrollment 139
Est. completion date July 8, 2021
Est. primary completion date June 13, 2021
Accepts healthy volunteers No
Gender All
Age group N/A to 3 Weeks
Eligibility Inclusion Criteria: 1. Very preterm infants born between gestational age 26 + 0 and 30 + 6 weeks (from the first day of the mother's last menstrual period and/or based on fetal ultrasound) 2. DM is given at the unit when MM is absent (or insufficient in amount) 3. Infants judged by the attending physician to be in need of nutrient fortification, as added in the form of HMF to MM and/or DM 4. Signed parental consent Exclusion Criteria: 1. Major congenital anomalies and birth defects 2. Infants who have had gastrointestinal surgery prior to randomization 3. Infants who have received IF prior to randomization

Study Design


Intervention

Dietary Supplement:
Bovine Colostrum
Infants randomized to the intervention group will receive a maximum of 2.8 g bovine colostrum (BC, Biofiber, Gesten, Denmark), as the HMF added to 100 ml of MM and/or DM, when EN has reached a dose of 80-100 ml/kg/d. The infants start with 1 g (0.5 g protein) BC per 100 ml human milk on the first day, increased to 2 g (1.0 g protein) on day 3, and finally 2.8 g (1.4 g protein) on day 5 if the infants only receive DM. The intervention lasts until the infants reach postmenstrual age (PMA) 35+6 weeks or in no-need of fortification due to sufficient growth, whichever comes first.
FM85
Infants randomized to the control group will receive a maximum of 4 g PreNAN FM85 (Nestlé, Vevey, Switzerland) as HMF, added to 100 ml MM and/or DM, when EN has reached a dose of 80-100 ml/kg/d. The infants starts with 1 g (0.35 g protein) FM85 per 100 ml human milk on the first day, which will be increased to 3 g (1.05 g protein) on day 3 and finally 4 g (1.4 g protein) on day 5, if the infants only receive DM. The infants will receive FM85 as the HMF as long as additional protein in the milk is needed until discharge.

Locations

Country Name City State
China Shenzhen Nanshan People's Hospital Shenzhen
China Shenzheng Baoan Maternity and Child Healthcare Hospital (SBMCH) Shenzhen Guangdong

Sponsors (1)

Lead Sponsor Collaborator
Per Torp Sangild

Country where clinical trial is conducted

China, 

Outcome

Type Measure Description Time frame Safety issue
Other Volume of gastric residual Volume of aspirated gastric residuals in ml From birth to hospital discharge, or up to 14 weeks
Other Color of gastric residual The color of aspirated gastric residuals categorized into 7 colours From birth to hospital discharge, or up to 14 weeks
Other Incidence of bloody gastric residual Number of infants in each group have had blood in the gastric residual From birth to hospital discharge, or up to 14 weeks
Other Frequency of stool per day Frequency of stool passed each day From birth to hospital discharge, or up to 14 weeks
Other Amount of the stool Using a 4-level pre-defined scale Amount of stool on the diaper: the percentage of area covered by stool on the diaper.
1 smear;
2 up to 25%;
3 25-50%;
4 >50%
From birth to hospital discharge, or up to 14 weeks
Other Color of the stool The color of stools categorized into 6 colors From birth to hospital discharge, or up to 14 weeks
Other Consistency of the stool Using a 4-level pre-defined scale From birth to hospital discharge, or up to 14 weeks
Other Total daily volume of enteral nutrition (EN) and parenteral nutrition (PN) Volume of EN (including MM, DM, infant formula, and fortification) and PN in take From birth to hospital discharge, or up to 14 weeks
Other Levels of macronutrients intake from EN and PN Calculated based on the volume and composition of EN and PN From birth to hospital discharge, or up to 14 weeks
Primary Incidence of feeding intolerance Number of infants in each group diagnosed with feeding intolerance for at least once. Feeding intolerance is defined as any pause of fortification or withhold of enteral feeding. From start of intervention until the infants reach PMA 35+6 weeks or are not in need of fortification due to sufficient growth, whichever comes first
Secondary Body weight Weight gain in grams per kg body weight from birth to discharge. Weight at different time points will be calculated into z-scores according to a reference. Delta z-scores will be used to evaluate growth and for comparison between groups. Measured weekly from the start of intervention until hospital discharge, or up to 14 weeks
Secondary Body length Recorded as a measure of growth in cm by standardized measuring procedures Measured weekly from the start of intervention until hospital discharge, or up to 14 weeks
Secondary Head circumference Recorded as a measure of head growth in cm by standardized measuring procedures Measured weekly from the start of intervention until hospital discharge, or up to 14 weeks
Secondary Incidence of necrotizing entercolitis (NEC) Number of infants in each group diagnosed with necrotizing enterocolitis (NEC) defined as Bell's stage II or above (Kliegman & Walsh 1987) From the start of intervention to hospital discharge, or up to 14 weeks
Secondary Incidence of late-onset sepsis (LOS) Number of infants in each group diagnosed with late-onset sepsis defined as clinical signs of infection >2 days after birth with antibiotic treatment for =5 days (or shorter than 5 days if the participant died) with or without one positive bacterial culture in blood or cerebral spinal fluid (CSF) From the start of intervention to hospital discharge, or up to 14 weeks
Secondary Time to reach full enteral feeding Number of days to full enteral feeding is reached - defined as the time when >150 ml/kg/d is reached and parenteral nutrition has been discontinued From birth to hospital discharge, or up to 14 weeks
Secondary Days on parenteral nutrition Number of days that the infant receives intravenous intakes of protein and/or lipid and/or glucose From birth to hospital discharge, or up to 14 weeks
Secondary Length of hospital stay Number of days in hospital, defined as days from birth until final discharge From birth to hospital discharge, or up to 14 weeks
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