- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03085277
Bovine Colostrum for Preterm Newborns (PreColos-RCT)
Bovine Colostrum Versus Preterm Formula as the First Supplemental Nutrition for Very Preterm Infants, a Randomized, Controlled Trial
Study Overview
Status
Intervention / Treatment
Detailed Description
The Precolos-RCT is a multicenter, two-arm, unblinded, randomized, controlled trial. Infants are randomized to an intervention group which receives BC and a control group which receives PF. In detail, MM is always the first priority, when available. When MM is not available, or the available amounts do not fulfill the needs, infants in BC group will receive BC and control infants will receive PF, as the supplementary diets. Feeding should be initiated within 24-48 h after birth following a pre-defined nutritional guideline. BC intervention should not exceed postnatal day 14. After the intervention period, the participants in both groups will receive standard feeding which is the available MM with or without supplemental preterm infant formula. Infants will be followed until discharge home or reach a postconceptional age of 37 weeks, whichever comes first (discharge home/37 wks).
In general, parenteral and enteral nutrition should be given according to the following description:
Parenteral and enteral nutrition will be given according to the targeted daily fluid, energy, and protein levels suggested by ESPGHAN and CSPEN. Enteral nutrition should be given according to the feeding guideline and PN is used to ensure the targeted protein, energy, and lipid intake when enteral feeding is insufficient to provide fluid and nutrition. Participating hospitals should try their best to assist mothers in expressing their colostrum and milk and giving mother's colostrum as the first feeds. Enteral feeding should be given as soon as possible within 24h of life after randomization for infants with BW > 750g. For infants with BW ≤ 750 g, first feeding should be given within 24 h if mother's colostrum is available. Otherwise, first feeding should wait until day 2 for mothers to express their own colostrum. Mother's colostrum and MM is given as much as available, and when it is not available or in an insufficient amount, BC or PF is used during the intervention period to supplement the lacking volume. Infants should receive an initial feeding volume of 5-10 ml/kg/d and the volume should increase by 5-20 ml/kg/d until 150-160 ml/kg/d depending on their BW. The advancing rate of feeding should follow the suggested pace but also be adjusted according to the tolerability of the infants. If feeding intolerance occurs, feeding should be at a flat rate or be withheld according to predefined criteria in 'parenteral and enteral nutrition SOP'. If infants can tolerate more, feeding can be increased faster. Since total protein intake should be within 4-4.5 g/kg/d according to the ESPGHAN guideline25, the maximal daily volume of BC should be calculated based on the available volume of MM and protein levels in MM and BC. The protein supply from MM is calculated assuming a protein content of 1.5 g/100 mL27 (during the first 14 days) and the protein supply from colostrum is 8 g/100 mL (may adjust to changes according to the product specification of the batch in use when the difference is bigger than 5%). At the end of the intervention period, the enteral feeding in the intervention group will be gradually transferred to standard feeding (MM with supplemental PF when needed). Participants in the control group will keep receiving standard feeding after the intervention period. However, if a participant reaches term during their hospital stay, PF may be changed to term formulas according to local guidelines. The participating hospitals use four types of PF with similar nutrients composition and will remain the same throughout the study.
Although in the intervention group, infants should receive supplemental BC instead of PF during the intervention period, there is a possibility that PF and BC are simultaneously used as the supplemental diets. For example, when a participant in the intervention group can tolerate a higher EN volume than the available volume of MM plus the maximum daily volume of BC (due to max protein limitation), PF needs to be given to fulfill the total EN volume. Importantly, the volume of each milk diet will need to be adjusted according to the maximal protein intake of 4-4.5 g/kg/d. When BC intake has reached the maximal volume due to protein limitation but fluid requirement still needs to be fulfilled by PN, the PN should be given with an amino acid level of 0.5 g/kg/d (other nutrients are provided accordingly)and BC volume should be reduced by 6.25 ml/kg/d. A detailed guideline for parenteral and enteral nutrition is described in an SOP: 'Parenteral and enteral nutrition SOP'.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Guangdong
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Dongguan, Guangdong, China
- Dongguan Women and Children's Hospital
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Foshan, Guangdong, China
- Foshan Maternal and Child Health Hospital
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Guangzhou, Guangdong, China
- The Sixth Affiliated Hospital of Sun Yat-sen University
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Shenzhen, Guangdong, China
- ShenZhen People's Hospital
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Shenzhen, Guangdong, China
- Longgang District Central Hospital of Shenzhen
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Shenzhen, Guangdong, China
- Shenzhen Luohu Maternal and Child Health Hospital
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Shenzhen, Guangdong, China
- Shenzhen Nanshan Maternal and Child Health Hospital
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Shenzhen, Guangdong, China
- University of Chinese Academy of Sciences-Shenzhen Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Preterm infants with gestational age between 26+0 and 31+6 weeks
- Delivered at participating hospitals or transferred from other hospitals within 24 h of age
- Signed parental consent
Exclusion Criteria:
- Major congenital anomalies or birth defects
- Congenital infection defined as suspected TORCHES infections: Toxoplasmosis, Rubella, CMV, Herpes, Hepatitis, Coxcackie, Syphilis, Varicella Zoster, HIV, Parvo B19
- Perinatal asphyxia with blood pH < 7.0 (umbilical or first neonatal)
- Extremely small for gestational age (birth weight z-score ≤ - 3)
- No realistic hope of immediate survival
- Has received any formula feeding prior to randomization
Study Plan
How is the study designed?
Design Details
- Primary Purpose: SUPPORTIVE_CARE
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: DOUBLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
ACTIVE_COMPARATOR: Preterm Formula
MM is always the first priority, when available.
When MM is not available, or the available amounts do not fulfill the needs, infants in this group will receive preterm formula, as the supplementary diets following the standard feeding guidelines in the participating hospitals.
|
Preterm formula is a type of infant formula designed for preterm infants.
It is used when mother's own milk is not available or not in sufficient amount as the enteral feeding for preterm infants in hospitals that do not have donor human milk.
|
EXPERIMENTAL: Bovine Colostrum
MM is always the first priority, when available.
When MM is not available, or the available amounts do not fulfill the needs, infants in this group will receive Bovine Colostrum (BC), as the supplementary diets.
BC feeding follows the same guideline as the control group in terms of initiation time (within 24-48h of age) and volume (5-10 ml/kg) and advancing rate (5-20 ml/kg/d).
BC intervention should not exceed postnatal day 14.
|
Bovine colostrum (BC) is the first milk from cows after birth and we suggest that BC may be used to supplement MM, instead of infant formula or DM.
BC is a rich source of protein (up to 150 g/L) and bioactive components, including lactoferrin, lysozyme, lactoperoxidase, immunoglobulins, and various growth factors, such as, IGF-I and -II, EGFs, and TGF-β.
BC has repeatedly been shown to have beneficial effects in a well-established piglet model of preterm infants, using various feeding regimens, including a gradual regimen that would mimic enteral feeding for preterm infants without access to MM during the first week.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to full enteral feeding
Time Frame: From the start of intervention until discharge home or reach a postconceptional age of 37 weeks, whichever comes first
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Full feeding volume is defined as the first day a participant receives 120 ml/kg/d for a consecutive period of 72 hours.
|
From the start of intervention until discharge home or reach a postconceptional age of 37 weeks, whichever comes first
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Combined incidence of severe neonatal infections (NEC, LOS, Meningitis) and mortality
Time Frame: From the start of intervention until discharge home or reach a postconceptional age of 37 weeks, whichever comes first
|
LOS: defined as one positive bacterial culture in blood occurring > 3 days after birth with clinical signs of infection and with antibiotics treatment for ≥ 5 days. Clinical sepsis: Negative bacterial culture in blood, but the infants have clinical signs of infection and fulfil more than 2 of the following criteria: (1) Decrease in WBC , or increase in WBC(2) Immature//total neutrophils ≥0.16; (3) CRP ≥8 μg/mL; (4) Procalcitonin ≥ 2 ng/mL; (5) Platelets ≤ 100 ×109/ L. Meningitis: Positive bacterial culture from cerebrospinal fluid (CSF) with clinical signs. When negative, if the infants have clinical signs of meningitis and have the following changes in leucocyte counts or biochemistry values in CSF: 1) increase in leucocytes, 2) increase in total protein, and 3) increase in glucose, clinical meningitis should be recorded. NEC: Stage II or III according to modified Bell's criteria |
From the start of intervention until discharge home or reach a postconceptional age of 37 weeks, whichever comes first
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The presence of feeding intolerance
Time Frame: From the start of intervention until discharge home or reach a postconceptional age of 37 weeks, whichever comes first
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Presence of feeding intolerance is defined as at any time when feeding is withheld by the neonatologists from day 1-7 and from day 8-14.
The number of withheld meals of the prescribed feeding volume, and actually received volume from day 1-7 and from day 8-14, are recorded to indicate the degree of feeding intolerance.
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From the start of intervention until discharge home or reach a postconceptional age of 37 weeks, whichever comes first
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Volume and color of gastric residual
Time Frame: From the start of intervention until discharge home or reach a postconceptional age of 37 weeks, whichever comes first
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The volume and color of gastric residuals withdrawn from the gastric tube are recorded by attending nurses, prior to a feeding
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From the start of intervention until discharge home or reach a postconceptional age of 37 weeks, whichever comes first
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Days on PN
Time Frame: From the start of intervention until discharge home or reach a postconceptional age of 37 weeks, whichever comes first
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Days on PN are the total number of days that a participant receives any i.v. protein and/or lipid.
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From the start of intervention until discharge home or reach a postconceptional age of 37 weeks, whichever comes first
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Days to regain birth weight
Time Frame: From the start of intervention until discharge home or reach a postconceptional age of 37 weeks, whichever comes first
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Days to regain birth weight is the total number of days that an infant used to regain his/her birth weight
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From the start of intervention until discharge home or reach a postconceptional age of 37 weeks, whichever comes first
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Days of hospitalization
Time Frame: From the start of intervention until discharge home or reach a postconceptional age of 37 weeks, whichever comes first
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Total number of days that a participant is hospitalized in the neonatal department for
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From the start of intervention until discharge home or reach a postconceptional age of 37 weeks, whichever comes first
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Body weight, length, and head circumference
Time Frame: Weekly until discharge home or reach a postconceptional age of 37 weeks, whichever comes first
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The weight, length, and head circumference of participants are measured every week
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Weekly until discharge home or reach a postconceptional age of 37 weeks, whichever comes first
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Blood tests on day 7 and 14 (extracted from patient charts)
Time Frame: Postnatal day 7 and 14
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Blood tests are performed according to the standard practices at each hospital, including blood gas, hematology, CRP, blood biochemistry for liver and kidney functions, bone health (e.g.
phosphate and bone-specific alkaline phosphatase), mineral status (including sodium, potassium, calcium, chloride, and phosphate), blood lipid profile, and blood glucose.
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Postnatal day 7 and 14
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Per Sangild, PhD, University of Copenhagen
Publications and helpful links
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Infections
- Systemic Inflammatory Response Syndrome
- Inflammation
- Gastrointestinal Diseases
- Infant, Newborn, Diseases
- Gastroenteritis
- Intestinal Diseases
- Sepsis
- Pregnancy Complications
- Obstetric Labor Complications
- Obstetric Labor, Premature
- Premature Birth
- Enterocolitis
- Enterocolitis, Necrotizing
- Neonatal Sepsis
Other Study ID Numbers
- Precolos-RCT
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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