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

Zinc Deficiency Clinical Trial

— ZnVeryPT  

Official title:

Higher and Standard Doses of Enteral Zinc Supplementation in Very Preterm Infants: A Randomized Controlled Trial

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT06219525
• Other study ID #: 66-451-1-1
• Secondary ID: 66-451-1-1
• Status: Enrolling by invitation
• Phase: N/A
• Start date: April 2, 2024
• Est. completion date: December 31, 2027

Study information

• Verified date: April 2024
• Source: Prince of Songkla University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 120
• Est. completion date: December 31, 2027
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Premature Birth
• Very Preterm Infants
• Zinc Deficiency

Intervention

Dietary Supplement:
• Higher dose of enteral zinc
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.
• Standard dose of enteral zinc
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.

Locations

Country	Name	City	State
Thailand	Songklanagarind Hospital, Prince of Songkla University	Hat-Yai	Songkhla

Sponsors (1)

Lead Sponsor	Collaborator
Prince of Songkla University

Country where clinical trial is conducted

Thailand, 

References & Publications (3)

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. — View 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. 2023 Nov 8. doi: 10.1055/s-0043-1776762. Online ahead of print. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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	Growth at 24 months postnatal age (PNA)	Growth [at 24 months PNA, 20-24 months corrected age]) was assessed by corrected age	At 24 months PNA (20-24 months corrected age)
Secondary	Neurodevelopment at 24 months postnatal age (PNA)	Neurodevelopmental outcomes (Bayley-III tests, were evaluated by only dedicated clinical psychologists at 24 months PNA [20-24 months corrected age]) were assessed by corrected age	At 24 months PNA (20-24 months corrected age)