Bovine Colostrum for Preterm Newborns (PreColos-RCT)
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|ClinicalTrials.gov Identifier: NCT03085277|
Recruitment Status : Recruiting
First Posted : March 21, 2017
Last Update Posted : February 13, 2020
|Condition or disease||Intervention/treatment||Phase|
|Enteral Feeding Intolerance Necrotizing Enterocolitis Late-Onset Neonatal Sepsis||Dietary Supplement: Bovine Colostrum Dietary Supplement: Preterm Formula||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||350 participants|
|Intervention Model:||Parallel Assignment|
|Intervention 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 (Participant, Outcomes Assessor)|
|Primary Purpose:||Supportive Care|
|Official Title:||Bovine Colostrum Versus Preterm Formula as the First Supplemental Nutrition for Very Preterm Infants, a Randomized, Controlled Trial|
|Actual Study Start Date :||July 1, 2017|
|Estimated Primary Completion Date :||August 31, 2020|
|Estimated Study Completion Date :||December 31, 2020|
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.
Dietary Supplement: Preterm Formula
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.
Dietary Supplement: Bovine Colostrum
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.
- 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.
- 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
- 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 ]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.
- 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 ]The volume and color of gastric residuals withdrawn from the gastric tube are recorded by attending nurses, prior to a feeding
- 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 on PN are the total number of days that a participant receives any i.v. protein and/or lipid.
- 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 to regain birth weight is the total number of days that an infant used to regain his/her birth weight
- Days of hospitalization [ Time Frame: From the start of intervention until discharge home or reach a postconceptional age of 37 weeks, whichever comes first ]Total number of days that a participant is hospitalized in the neonatal department for
- Body weight, length, and head circumference [ Time Frame: Weekly until discharge home or reach a postconceptional age of 37 weeks, whichever comes first ]The weight, length, and head circumference of participants are measured every week
- Routine blood tests [ Time Frame: On postnatal day 7 and 14 ]Blood tests (arteries blood) 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, magnesium, chloride, and phosphate), blood lipid profile, blood glucose, and immunoglobulin profile. The purpose is to monitor metabolic acidosis, infection, liver and kidney functions, bone health, and nutritional status in order to discover the possible safety risks or benefits of this BC intervention.
- Plasma amino acid profile [ Time Frame: On postnatal day 7 and 14 ]Plasma amino acid profile is analyzed by mass spectrophotometry to investigate whether BC feeding provides a normal range of plasma amino acid pattern. Plasma citrulline concentration is considered as a biomarker for absorptive enterocyte mass and/or function.
- Microbiota composition in feces [ Time Frame: On postnatal day 7 and 14 and at 1st and 2nd month. ]Fecal microbiota Is determined using high through-put sequencing technique to investigate whether the BC diet will affect the microbiota composition which is believed to be important for gut development and immunity, and to prevent overgrowth with pathogenic bacteria.
- Levels of plasma markers [ Time Frame: On postnatal day 7 and 14 ]Levels of markers of the gut and systemic inflammation analyzed by untargeted and/or targeted proteomics or immune assays (e.g. NET-components, cell-free DNA, DNA-bound histone, lactoferrin, calprotectin, intestinal fatty acid binding protein) in relation to NEC and sepsis
- Levels of whole blood markers [ Time Frame: On postnatal day 7, 14, and 28 ]Levels of markers of gut and systemic inflammation will be analyzed by transcriptomics and/or epigenetics using dried whole blood collected on filter papers, and related to NEC and sepsis
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03085277
|Contact: Per Sangild, PhD||+45 35 33 26 email@example.com|
|Contact: Yanqi Li, PhD||+45 firstname.lastname@example.org|
|Dongguan Women and Children's Hospital||Recruiting|
|Dongguan, Guangdong, China|
|Contact: Yong Yang|
|Contact: Minxu Li|
|Foshan Maternal and Child Health Hospital||Recruiting|
|Foshan, Guangdong, China|
|Contact: Yiheng Dai email@example.com|
|Contact: Xiaoyan Gao firstname.lastname@example.org|
|Principal Investigator: Yiheng Dai|
|Sub-Investigator: Xiaoyan Gao|
|The Sixth Affiliated Hospital of Sun Yat-sen University||Recruiting|
|Guangzhou, Guangdong, China|
|Contact: Hu Hao email@example.com|
|Contact: Fei Ma firstname.lastname@example.org|
|Principal Investigator: Hu Hao|
|Sub-Investigator: Mengxian Liu|
|Longgang District Central Hospital of Shenzhen||Recruiting|
|Shenzhen, Guangdong, China|
|Contact: Huixian Qiu email@example.com|
|Contact: Xunbin Huang firstname.lastname@example.org|
|Principal Investigator: Huixian Qiu|
|Sub-Investigator: Xunbin Huang|
|Sub-Investigator: Shujuan Zeng|
|Shenzhen Guangming People's Hospital||Not yet recruiting|
|Shenzhen, Guangdong, China|
|Contact: Zhenzhi Ye email@example.com|
|Contact: Xiaoli Chen firstname.lastname@example.org|
|Principal Investigator: Zhenzhi Ye|
|Sub-Investigator: Xiaoli Chen|
|Shenzhen Luohu Maternal and Child Health Hospital||Recruiting|
|Shenzhen, Guangdong, China|
|Contact: Yuefeng Li email@example.com|
|Contact: Xuelei Gong firstname.lastname@example.org|
|Principal Investigator: Yuefeng Li|
|Sub-Investigator: Xuelei Gong|
|Shenzhen Nanshan Maternal and Child Health Hospital||Recruiting|
|Shenzhen, Guangdong, China|
|Contact: Luanying Tian email@example.com|
|Contact: Xiujuan Wu firstname.lastname@example.org|
|Principal Investigator: Luanying Tian|
|Sub-Investigator: Xiujuan Wu|
|Shenzhen People's Hospital||Recruiting|
|Shenzhen, Guangdong, China|
|Contact: Benqing Wu +86 139 0243 6593 email@example.com|
|Contact: Lu Ding +86 13922851709 firstname.lastname@example.org|
|Principal Investigator: Benqing Wu|
|Sub-Investigator: Ding Lu|
|Sub-Investigator: Jinzhen Su|
|Zhuhai Maternal and Child Health Care Hospital||Not yet recruiting|
|Zhuhai, Guangdong, China|
|Contact: Huiwen Huang|
|Contact: Luoying Huo|
|Study Chair:||Per Sangild, PhD||University of Copenhagen|