Higher and Standard Doses of Enteral Zinc Supplementation in Very Preterm Infants

NCT06219525 | Recruiting

• 1 other identifier: 66-451-1-1
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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

Conditions

Very Preterm Infants; Zinc Deficiency

Keywords

Growth and Development; Mortality; Newborn; Premature Infant; Zinc

Outcome Measures

Primary Outcomes (3)

• 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)

  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

  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 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

  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)

• 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)

  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

  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 (2)

• 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)

Study Arms (2)

Higher dose of enteral zinc

ACTIVE COMPARATOR

higher dose of zinc sulfate 10 mg/day; each 1 mL contains 10 mg of elemental zinc (osmolality 450 Osm/kg H2O).

Dietary Supplement: Higher dose of enteral zinc

Standard dose of enteral zinc

PLACEBO COMPARATOR

standard dose of zinc sulfate 1 mg/day; each 1 mL contains 1 mg of elemental zinc (osmolality 45 Osm/kg H2O).

Dietary Supplement: Standard dose of enteral zinc

Interventions

Higher dose of enteral zinc DIETARY_SUPPLEMENT

Higher dose of zinc sulfate 10 mg/day; each 1 mL contains 10 mg of elemental zinc (osmolality 450 Osm/kg H2O). After randomization, nurses blinded to the study aims administered the assigned preparation 1 mL via tuberculin syringe, once daily, 1 hour after feeding. Zinc sulphate oral solution was prepared by the pharmaceutical compounding unit in the hospital. The supplement was given again to subjects who vomited within 15 minutes after the administration. All episodes of vomiting were reported on the record form. Vomiting episodes within 15 minutes were recorded. The supplement assigned was at discharge or at 44 weeks of postmenstrual age whichever came first. Both groups received multivitamin (MTV) products and iron supplement as routine preterm care.

Higher dose of enteral zinc

Standard dose of enteral zinc DIETARY_SUPPLEMENT

Standard dose of zinc sulfate 1 mg/day; each 1 mL contains 1 mg of elemental zinc (osmolality 45 Osm/kg H2O). After randomization, nurses blinded to the study aims administered the assigned preparation 1 mL via tuberculin syringe, once daily, 1 hour after feeding. Zinc sulphate oral solution was prepared by the pharmaceutical compounding unit in the hospital. The supplement was given again to subjects who vomited within 15 minutes after the administration. All episodes of vomiting were reported on the record form. Vomiting episodes within 15 minutes were recorded. The supplement assigned was discontinued at discharge or at 44 weeks of postmenstrual age whichever came first. Both groups received multivitamin (MTV) products and iron supplement as routine preterm care.

Standard dose of enteral zinc

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Prince of Songkla University: lead

Study Sites (1)

Songklanagarind Hospital, Prince of Songkla University

Hat Yai, Changwat Songkhla, 90110, Thailand

RECRUITING

Related Publications (3)

• 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.

  PMID: 37939725 BACKGROUND

• 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.

  PMID: 21546443 BACKGROUND

• 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.

  PMID: 24025633 BACKGROUND

MeSH Terms

Conditions

Premature Birth

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Study Officials

• Anucha Thatrimontrichai, MD

  Prince of Songkla University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anucha Thatrimontrichai, MD

CONTACT

+66 954300690; tanucha@medicine.psu.ac.th

Boonwiroj Jitwilertrat, MD

CONTACT

+66 914953851; Boonwiroj@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associated professor

Model Details: 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.

Study Record Dates

• First Submitted: December 25, 2023
• First Posted: January 23, 2024
• Study Start: April 2, 2024
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2027
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

TH (1)