Clinical trial NCT06219525: Higher and Standard Doses of Enteral Zinc Supplementation in Very Preterm Infants
Official title: Higher and Standard Doses of Enteral Zinc Supplementation in Very Preterm Infants: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Very Preterm Infants
Zinc Deficiency
Keywords: Growth and Development
Mortality
Newborn
Premature Infant
Zinc
Lead sponsor: Prince of Songkla University
Sponsor class: OTHER
First posted: 2024-01-23
Enrollment: 120
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study design was approved by the ethics committee of our Center. Written informed consent was obtained from the parents of the infants enrolled in the study. Stratification was performed based on birthweight \[BW\] (401-999 or 1,000-1,499 or 1,500-1800 grams) and small for gestational age (yes or no). Participants were randomly allocated (1:1) to one of two treatments (higher or standard doses of zinc supplement). The allocation sequence was performed via computer generation, with permuted block and kept as consecutive numbers by statistician. Allocation concealment was ensured by using identical, opaque, and sealed envelopes.
Primary purpose: TREATMENT

Brief summary: 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

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: 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)
timeFrame: 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)
measure: 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)
timeFrame: 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)
measure: 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)
timeFrame: 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)
Secondary outcomes:
measure: Growth at 24 months postnatal age (PNA)
timeFrame: At 24 months PNA (20-24 months corrected age)
measure: Neurodevelopment at 24 months postnatal age (PNA)
timeFrame: At 24 months PNA (20-24 months corrected age)
Other outcomes:
Locations:
city: Hat-Yai
country: Thailand
facility: Songklanagarind Hospital, Prince of Songkla University
state: Songkhla
Study officials:
affiliation: Prince of Songkla University
name: Anucha Thatrimontrichai, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sahin S, Sari FN, Bidev D, Bozkurt O, Dizdar EA, Oguz SS. Zinc Supplementation in Very Low Birth Weight Infants: A Randomized Controlled Trial. Am J Perinatol. 2024 May;41(S 01):e3107-e3114. doi: 10.1055/s-0043-1776762. Epub 2023 Nov 8.
citation: Ram Kumar TV, Ramji S. Effect of zinc supplementation on growth in very low birth weight infants. J Trop Pediatr. 2012 Feb;58(1):50-4. doi: 10.1093/tropej/fmr036. Epub 2011 May 5.
citation: Terrin G, Berni Canani R, Passariello A, Messina F, Conti MG, Caoci S, Smaldore A, Bertino E, De Curtis M. Zinc supplementation reduces morbidity and mortality in very-low-birth-weight preterm neonates: a hospital-based randomized, placebo-controlled trial in an industrialized country. Am J Clin Nutr. 2013 Dec;98(6):1468-74. doi: 10.3945/ajcn.112.054478. Epub 2013 Sep 11.