Enteral Feeding IntolerancePreColos-RCTNCT03085277
Bovine Colostrum for Preterm Newborns
A study testing Bovine Colostrum and Preterm Formula in people with Enteral Feeding Intolerance and Necrotizing Enterocolitis, run by Per Torp Sangild at 8 sites in China.
Trial summary
Feeding intolerance is a common problem in very preterm infants due to their immature digestive system. This intolerance extends the time to full enteral feeding and thereby also prolongs the time on parenteral nutrition (PN). Read more about this study
- Who is it for?
- Ages Up to 2 days
- Conditions the study is for
- Enteral Feeding Intolerance, Necrotizing Enterocolitis, Late-Onset Neonatal Sepsis
- What is being tested?
- Bovine Colostrum and Preterm Formula
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 350 participants
- Where
- 8 sitesChina
- Study dates
- 1 Jul 2017to 18 Nov 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 2 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
China8 sites
Dongguan Women and Children's Hospital
Dongguan, Guangdong
Foshan Maternal and Child Health Hospital
Foshan, Guangdong
The Sixth Affiliated Hospital of Sun Yat-sen University
Guangzhou, Guangdong
Longgang District Central Hospital of Shenzhen
Shenzhen, Guangdong
Shenzhen Luohu Maternal and Child Health Hospital
Shenzhen, Guangdong
Shenzhen Nanshan Maternal and Child Health Hospital
Shenzhen, Guangdong
Shenzhen People's Hospital
Shenzhen, Guangdong
University of Chinese Academy of Sciences-Shenzhen Hospital
Shenzhen, Guangdong
About this study
Official title: Bovine Colostrum Versus Preterm Formula as the First Supplemental Nutrition for Very Preterm Infants, a Randomized, Controlled Trial
Feeding intolerance is a common problem in very preterm infants due to their immature digestive system. This intolerance extends the time to full enteral feeding and thereby also prolongs the time on parenteral nutrition (PN). Prolonged time to full enteral feeding may predispose these infants to a higher risk of growth retardation, infections and organ dysfunctions (e.g. liver, brain). Mother's own milk (MM) is considered the optimal nutrition for preterm infants and is superior to infant formula (including preterm formula, PF) in stimulating gut maturation, feeding tolerance, resistance against necrotizing enterocolitis (NEC) and late-onset sepsis (LOS), and long-term neurodevelopmental outcomes. However, MM is often absent, or not available in sufficient amounts, during the first days or weeks after preterm delivery. Human donor milk (DM) is probably a better supplement to MM than PF, but DM is not available for all hospitals. To supplement insufficient MM during the early neonatal period in hospital settings with no access to donor milk, we suggest that bovine colostrum (BC) may be used instead of PF for very preterm infants during early life. BC, the first milk from cows after birth, is a rich source of protein 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 improve gut maturation and NEC/LOS resistance in a well-established piglet model of preterm infants. We suggest a randomized, controlled trial to investigate the effects of BC vs. PF, supplemented to MM during the first 2 weeks, on the time to full enteral feeding in very preterm infants.
Read the 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'.
- Being tested
- Bovine Colostrum, Preterm Formula
- Keywords
- Bovine colostrum, Preterm formula, Very preterm infants, Enteral feeding
- Medical subject headings
- Enterocolitis, Necrotizing, Neonatal Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bovine ColostrumDietary supplement
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.
Preterm FormulaDietary supplement
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.
| Study group | Role | What they receive |
|---|---|---|
| Preterm Formula | Active comparator | 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. Receives: Dietary Supplement: Preterm Formula |
| Bovine Colostrum | Experimental | 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. Receives: Dietary Supplement: Bovine Colostrum |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to full enteral feeding
Full feeding volume is defined as the first day a participant receives 120 ml/kg/d for a consecutive period of 72 hours.
Measured: From the start of intervention until discharge home or reach a postconceptional age of 37 weeks, whichever comes first
Secondary outcomes (8)
Combined incidence of severe neonatal infections (NEC, LOS, Meningitis) and mortality
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
Measured: From the start of intervention until discharge home or reach a postconceptional age of 37 weeks, whichever comes first
The presence of feeding intolerance
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.
Measured: From the start of intervention until discharge home or reach a postconceptional age of 37 weeks, whichever comes first
Volume and color of gastric residual
The volume and color of gastric residuals withdrawn from the gastric tube are recorded by attending nurses, prior to a feeding
Measured: From the start of intervention until discharge home or reach a postconceptional age of 37 weeks, whichever comes first
Days on PN
Days on PN are the total number of days that a participant receives any i.v. protein and/or lipid.
Measured: From the start of intervention until discharge home or reach a postconceptional age of 37 weeks, whichever comes first
Days to regain birth weight
Days to regain birth weight is the total number of days that an infant used to regain his/her birth weight
Measured: From the start of intervention until discharge home or reach a postconceptional age of 37 weeks, whichever comes first
Days of hospitalization
Total number of days that a participant is hospitalized in the neonatal department for
Measured: From the start of intervention until discharge home or reach a postconceptional age of 37 weeks, whichever comes first
Body weight, length, and head circumference
The weight, length, and head circumference of participants are measured every week
Measured: Weekly until discharge home or reach a postconceptional age of 37 weeks, whichever comes first
Blood tests on day 7 and 14 (extracted from patient charts)
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.
Measured: Postnatal day 7 and 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2017
- Study start1 Jul 2017
- Primary completion23 Oct 2020
- Study completion18 Nov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Enteral Feeding IntoleranceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- When a preterm infant is delivered at these hospitals or transferred from other hospitals on the day of birth, responsible neonatologists/PIs/co-PIs will evaluate the infant for its eligibility. If the infant fulfills the recruitment criteria, parent(s) are informed and explained about the study and asked for permission to recruit their babies. After confirmed consent, the infant will be, per hospital, randomized to two groups in a 1:1 ratio. Infants should be recruited and randomized as soon as possible after birth and no later than 48 h. The first supplemental enteral feeding (PF or BC) can be given as soon as the infants are randomized. Randomization will be stratified by birth weight \< 1000 g, birth weight ≥ 1000 g, and randomly permuted blocks of size 4 and 6 will be used. A random sequence list will be generated by computer software for each hospital and a corresponding sequence number can only be checked to see allocation after informed consent is given and the baby is enrolled.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 350 participants (actual)
Sponsor and investigators
- Lead sponsor
- Per Torp Sangild
- Sponsor type
- University, hospital or other
- Collaborators
- Sixth Affiliated Hospital, Sun Yat-sen University, Maternal and Child Health Hospital of Foshan, Shenzhen People's Hospital, Shenzhen Luohu Maternal and Child Health Hospital, Shenzhen Hospital (Guangming), University of Chinese Academy of Sciences, Longgang District People's Hospital of Shenzhen, Shenzhen Nanshan Maternity and Child Healthcare Hospital, Dongguan Women and Children's Hospital
- Responsible party
- Sponsor-investigator, Per Torp Sangild, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Per Sangild, PhD, Study chair, University of Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03085277
- Sponsor's protocol ID
- Precolos-RCT
- Acronym
- PreColos-RCT
- Status last verified
- Jul 2022
- First submitted
- 14 Mar 2017
- Last updated
- 12 Jul 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Yan X, Pan X, Ding L, Dai Y, Chen J, Yang Y, Li Y, Hao H, Qiu H, Ye Z, Shen RL, Li Y, Ritz C, Peng Y, Zhou P, Gao F, Jiang PP, Lin HC, Zachariassen G, Sangild PT, Wu B. Bovine colostrum to supplement the first feeding of very preterm infants: The PreColos randomized controlled trial. Clin Nutr. 2023 Aug;42(8):1408-1417. doi: 10.1016/j.clnu.2023.06.024. Epub 2023 Jun 28.
PubMed 37437359Juhl SM, Ye X, Zhou P, Li Y, Iyore EO, Zhang L, Jiang P, van Goudoever JB, Greisen G, Sangild PT. Bovine Colostrum for Preterm Infants in the First Days of Life: A Randomized Controlled Pilot Trial. J Pediatr Gastroenterol Nutr. 2018 Mar;66(3):471-478. doi: 10.1097/MPG.0000000000001774.
PubMed 29019855
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bovine Colostrum Versus Preterm Formula as the First Supplemental Nutrition for Very Preterm Infants, a Randomized, Controlled Trial
- ClinicalTrials.gov ID
- NCT03085277
- Acronym / sponsor ID
- PreColos-RCT / Precolos-RCT
- Keywords
- Bovine colostrum, Preterm formula, Very preterm infants, Enteral feeding
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 350 participants (actual)
- Lead sponsor
- Per Torp SangildUniversity, hospital or other
- Collaborators
- Sixth Affiliated Hospital, Sun Yat-sen University, Maternal and Child Health Hospital of Foshan, Shenzhen People's Hospital, Shenzhen Luohu Maternal and Child Health Hospital, Shenzhen Hospital (Guangming), University of Chinese Academy of Sciences, Longgang District People's Hospital of Shenzhen, Shenzhen Nanshan Maternity and Child Healthcare Hospital, Dongguan Women and Children's Hospital
- Study start
- 1 Jul 2017 (actual)
- Primary completion
- 23 Oct 2020 (actual)
- Study completion
- 18 Nov 2020 (actual)
- First posted
- 21 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Feeding intolerance is a common problem in very preterm infants due to their immature digestive system. This intolerance extends the time to full enteral feeding and thereby also prolongs the time on parenteral nutrition (PN). Prolonged time to full enteral feeding may predispose these infants to a higher risk of growth retardation, infections and organ dysfunctions (e.g. liver, brain). Mother's own milk (MM) is considered the optimal nutrition for preterm infants and is superior to infant formula (including preterm formula, PF) in stimulating gut maturation, feeding tolerance, resistance against necrotizing enterocolitis (NEC) and late-onset sepsis (LOS), and long-term neurodevelopmental outcomes. However, MM is often absent, or not available in sufficient amounts, during the first days or weeks after preterm delivery. Human donor milk (DM) is probably a better supplement to MM than PF, but DM is not available for all hospitals. To supplement insufficient MM during the early neonatal period in hospital settings with no access to donor milk, we suggest that bovine colostrum (BC) may be used instead of PF for very preterm infants during early life. BC, the first milk from cows after birth, is a rich source of protein 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 improve gut maturation and NEC/LOS resistance in a well-established piglet model of preterm infants. We suggest a randomized, controlled trial to investigate the effects of BC vs. PF, supplemented to MM during the first 2 weeks, on the time to full enteral feeding in very preterm infants.
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 design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- When a preterm infant is delivered at these hospitals or transferred from other hospitals on the day of birth, responsible neonatologists/PIs/co-PIs will evaluate the infant for its eligibility. If the infant fulfills the recruitment criteria, parent(s) are informed and explained about the study and asked for permission to recruit their babies. After confirmed consent, the infant will be, per hospital, randomized to two groups in a 1:1 ratio. Infants should be recruited and randomized as soon as possible after birth and no later than 48 h. The first supplemental enteral feeding (PF or BC) can be given as soon as the infants are randomized. Randomization will be stratified by birth weight < 1000 g, birth weight ≥ 1000 g, and randomly permuted blocks of size 4 and 6 will be used. A random sequence list will be generated by computer software for each hospital and a corresponding sequence number can only be checked to see allocation after informed consent is given and the baby is enrolled.
| Arm | Type | Receives |
|---|---|---|
| Preterm Formula | Active comparator | Dietary Supplement: Preterm FormulaMM 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. |
| Bovine Colostrum | Experimental | Dietary Supplement: Bovine ColostrumMM 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. |
Who may qualify
- Ages
- Up to 2 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bovine ColostrumBovine 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. | Dietary supplement | Bovine Colostrum |
| Preterm FormulaPreterm 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. | Dietary supplement | Preterm Formula |
Primary outcome
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
Full feeding volume is defined as the first day a participant receives 120 ml/kg/d for a consecutive period of 72 hours.
8 secondary outcomes
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
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
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
Days on PN
Time frame: From the start of intervention until discharge home or reach a postconceptional age of 37 weeks, whichever comes first
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
Days of hospitalization
Time frame: From the start of intervention until discharge home or reach a postconceptional age of 37 weeks, whichever comes first
Body weight, length, and head circumference
Time frame: Weekly until discharge home or reach a postconceptional age of 37 weeks, whichever comes first
Blood tests on day 7 and 14 (extracted from patient charts)
Time frame: Postnatal day 7 and 14
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2022.
- Derived from this study: PubMed 37437359Yan X, Pan X, Ding L, Dai Y, Chen J, Yang Y, Li Y, Hao H, Qiu H, Ye Z, Shen RL, Li Y, Ritz C, Peng Y, Zhou P, Gao F, Jiang PP, Lin HC, Zachariassen G, Sangild PT, Wu B. Bovine colostrum to supplement the first feeding of very preterm infants: The PreColos randomized controlled trial. Clin Nutr. 2023 Aug;42(8):1408-1417. doi: 10.1016/j.clnu.2023.06.024. Epub 2023 Jun 28.
- Derived from this study: PubMed 29019855Juhl SM, Ye X, Zhou P, Li Y, Iyore EO, Zhang L, Jiang P, van Goudoever JB, Greisen G, Sangild PT. Bovine Colostrum for Preterm Infants in the First Days of Life: A Randomized Controlled Pilot Trial. J Pediatr Gastroenterol Nutr. 2018 Mar;66(3):471-478. doi: 10.1097/MPG.0000000000001774.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Per Sangild, PhD study chair
University of Copenhagen
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Bovine Colostrum and Preterm Formula in people with Enteral Feeding Intolerance and Necrotizing Enterocolitis, run by Per Torp Sangild at 8 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03085277, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jul 2022.