Higher and Standard Doses of Enteral Zinc Supplementation in Very Preterm Infants: A Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 入组人数
- 120
- 试验地点
- 2
- 主要终点
- Weight velocity during the date of start intervention until the end of the time interval (at least 2 weeks of intervention on date of 44 weeks of postmenstrual age or discharge whichever came first)
研究概览
简要总结
The goal of this randomized clinical trial is to compare the effect of higher (10 mg per day) versus standard (1 mg per day) doses of zinc supplementation The main questions it aims to answer are:
- Growth velocities and delta z-scores during the date of start intervention until the end of the time interval (at least 2 weeks of intervention on date of 44 weeks of postmenstrual age or discharge whichever came first) in very preterm infants with a birthweight less than1800 grams.
- Growth and neurodevelopment at 24 months postnatal age
详细描述
After informed consent, the neonates enrolled were randomly allocated to two study groups: group A (higher dose of zinc sulfate 10 mg/day; each 1 mL contains 10 mg of elemental zinc; Pharmacy Division, Songklanagarind Hospital), and group B (standard dose of zinc sulfate 1 mg/day; each 1 mL contains 1 mg of elemental zinc; Pharmacy Division, Songklanagarind Hospital).
The zinc solution was available as a white powder in white opaque plastic container. When normal sterile water was added up to the indicator mark, it provided 60 mL of solution containing 10 mg/mL (osmolality 450 Osm/kg H2O) and 1 mg/mL (osmolality 45 Osm/kg H2O) of elemental zinc with similar color, taste and packing. The two doses of zinc preparations were provided in identical bottles and was labeled only zinc solution, hospital number and name-surname, without indication of group identity (A or B) or concentration by a neonatal registered pharmacist in the study center (only unblinded investigator who recorded the group allocation according to the randomization list in consecutive participant). This information was not available to the investigators during the data had been obtained, entered in the database, and analyzed by a blinded statistician.
After randomization, nurses blinded to the study aims administered the assigned preparation 1 mL via tuberculin syringe, once daily, 1 h after feeding. Zinc sulphate oral solution was prepared by the pharmaceutical compounding unit in the hospital. Each subject received a 60-mL bottle solution individually and continued the medication until finished, either at a concentration of 1 or 10 mg/mL, depending on the study group. The supplement was given again to subjects who vomited within 15 min after the administration. All episodes of vomiting were reported on the record form. Vomiting episodes within 15 min were recorded. The supplement assigned was discontinued at discharge or at 44 weeks' postmenstrual age whichever came first. Both groups received multivitamin products (1 mL/day) and iron supplement (2-3 mg/kg/day) as routine preterm care.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
盲法说明
The two doses of zinc preparations were provided in identical bottles without indication of group identity or content by a neonatal registered pharmacist (assigned participants to interventions, only unblinded investigator) in the study center. A dedicated nurse (enrolled participants, obtained informed consent, monitored intervention, and recorded data), registered nurses and attending neonatologists (did routine neonatal care), statistician (generated the allocation sequence), and dedicated clinical psychologist were blinded the allocation groups.
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Very preterm neonates (gestational age [GA]: 24 0/7-32 6/7 weeks and BW: 401-1800 grams) were consecutively admitted in the NICU and NMCU
- •Body weight at enrollment less than 800 grams
- •Stable neonates and full enteral feeding (150 mL/kg/day) at least for a few days
排除标准
- •Outborn neonate who was admitted in study center after 7 days of life
- •Congenital infections
- •Malformations, syndromes, or genetic defects
- •Evidence of culture proven sepsis or necrotizing enterocolitis or death diagnosed before enrollment
- •Gastrointestinal (GI) surgery or high GI fluid output (usually ileostomy losses)
- •Unstable neonate during weighing including on intercostal drainage tube or drainage
- •Neonates need diuretics more than 7 days
- •Severe birth asphyxia (5-minute Apgar score less than 4)
- •Parents' decision not to participate the study
结局指标
主要结局
Weight velocity during the date of start intervention until the end of the time interval (at least 2 weeks of intervention on date of 44 weeks of postmenstrual age or discharge whichever came first)
时间窗: during the date of start intervention until the end of the time interval (at least 2 weeks of intervention on date of 44 weeks of postmenstrual age or discharge whichever came first)
Weight velocity was calculated during the beginning of study (time1 \[T1\], Weight1 \[W1\]) until the end of the time interval (time2 \[T2\], Weight \[W2\]). Weight gain (grams per kilogram per day) was calculated during the period using the 2-point average method \[1000\*(W2-W1)\]/\[(W2+W1)/2)\*(T2-T1)\]. Weight delta z-scores of were calculated weight z-scores at T2 minus weight z-scores at T1 from the Fenton's Growth Chart
Length velocity during the date of start intervention until the end of the time interval (at least 2 weeks of intervention on date of 44 weeks of postmenstrual age or discharge whichever came first)
时间窗: during the date of start intervention until the end of the time interval (at least 2 weeks of intervention on date of 44 weeks of postmenstrual age or discharge whichever came first)
Length velocity was calculated during the beginning of study (time1 \[T1\], Length1 \[L1\]) until the end of the time interval (time2 \[T2\], Length \[L2\]). Length velocities (centimeters per kilogram per day) was calculated during the period using the 2-point average method \[1000\*(L2-L1)\]/\[(L2+L1)/2)\*(T2-T1)\] Length delta z-scores were calculated length z-scores at T2 minus length z-scores at T1 from the Fenton's Growth Chart
Head circumference (HC) velocity during the date of start intervention until the end of the time interval (at least 2 weeks of intervention on date of 44 weeks of postmenstrual age or discharge whichever came first)
时间窗: during the date of start intervention until the end of the time interval (at least 2 weeks of intervention on date of 44 weeks of postmenstrual age or discharge whichever came first)
HC velocity was calculated during the beginning of study (time1 \[T1\], HC1) until the end of the time interval (time2 \[T2\], HC2). HC velocities (centimeters per kilogram per day) was calculated during the period using the 2-point average method \[1000\*(HC2-HC1)\]/\[(HC2+HC1)/2)\*(T2-T1)\] HC delta z-scores were calculated HC z-scores at T2 minus HC z-scores at T1 from the Fenton's Growth Chart
次要结局
- Growth at 24 months postnatal age (PNA)(At 24 months PNA (20-24 months corrected age))
- Neurodevelopment at 24 months postnatal age (PNA)(At 24 months PNA (20-24 months corrected age))
研究者
Anucha Thatrimontrichai
Associated professor
Prince of Songkla University