Role of Oral Zinc in Reducing Neonatal Indirect Hyperbilirubinemia

NCT06227624 | Completed Phase 3 FDA Drug

• 1 other identifier: 00136/2018
• Study Type: interventional
• Target: 192
• Locations: 1 country
• Sites: 1

Brief Summary

This study aimed to determine the role of oral zinc in reducing the neonatal indirect hyperbilirubinemia if used concomitant with the standard phototherapy

Conditions

Neonatal Jaundice

Outcome Measures

Primary Outcomes (1)

• Determine the role of oral zinc in reducing level of unconjugated hyperbilirubinemia

  Measurement of serum bilirubin after receiving zinc/ phototherapy and phototherapy alone

  Baseline

Study Arms (2)

combined oral zinc salts with phototherapy

OTHER

neonates received combination therapy which is phototherapy and oral zinc sulfate in a dose of 5 mg every 12 hours using a calibrated dropper provided with the bottle, during the period of NICU admission of neonates on phototherapy

Drug: Oral zinc sulfate and standard phototherapy

phototherapy group

NO INTERVENTION

neonates receiving phototherapy alone

Interventions

Oral zinc sulfate and standard phototherapy DRUG

study the role of oral zinc sulfate in reducing level of indirect hyperbilirubinemia in neonates if used with standard phototherapy

Also known as: standard phototherapy alone

combined oral zinc salts with phototherapy

Eligibility Criteria

• Age: 1 Hour - 28 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Neonates with total serum bilirubin (TSB) exceeding the 40th percentile track for age as per the hour-specific bilirubin nomogram of the American Academy of Pediatrics (AAP)
• Neonates who have indirect hyperbilirubinemia, not indicated for exchange transfusion.

You may not qualify if:

• Neonates submitted to blood transfusion.
• Neonates indicated for exchange transfusion
• Associated congenital anomalies.
• Co-morbidities such as sepsis, pneumonia or respiratory distress.
• Neonates whom their mothers received phenobarbitone during the third trimester

Sponsors & Collaborators

• National Liver Institute, Egypt: lead

Study Sites (1)

National Liver Institute

Shibīn al Kawm, Menoufia, 32511, Egypt

Location

Related Publications (4)

• • Kumar A, Bagri NK, Basu S, Asthana RK. Zinc Supplementation for Neonatal Hyperbilirubinemia: A Randomized Controlled Trial. Indian Pediatrics . 2014; 51:375-378. • Watchko JF, Tiribelli C. Bilirubin-Induced Neurologic Damage- Mechanisms and Management Approaches. New England Journal of Medicine. 2013; 369:2021-2030. • Olusanya B O, Imam Z O, Emokpae A A, Iskander IF. Revisiting the criteria for exchange transfusion for severe neonatal hyperbilirubinemia in resource-limited settings. Neonatology. 2016; 109:97-104. • Cuperus F, Hafkamp A, Hulzebos C, Verkade H. Pharmacological therapies for unconjugated hyperbilirubinemia. Current pharmaceutical design. 2009; 15:2927-2938. • Prashanth GP. The Significance of Enterohepatic Circulation in the Causation Neonatal Hyperbilirubinemia. The Indian Journal of Pediatrics. 2012; 79:1251-1252. • Patil R, Sontakke T, Biradar A, Nalage D. Zinc: an essential trace element for human health and beyond. Food and Health. 2023; 5(3):13.

  BACKGROUND

• • Méndez-Sánchez N, Roldán-Valadez E, Flores M A, Cárdenas-Vázquez R, Uribe M. Zinc salts precipitate unconjugated bilirubin in vitro and inhibit enterohepatic cycling of bilirubin in hamsters. Eur J Clin Invest. 2001; 31(9):773-80. • Vitek L, Muchova L, Zelenka J, et al. The effect of zinc salts on serum bilirubin levels in hyperbilirubinemic rats. J Pediatr Gastroenterol Nutr. 2005; 40:135-140. • Méndez-Sánchez N, Martínez M, González V, Roldán-Valadez E, Flores M A Uribe M. Zinc sulfate inhibits the enterohepatic cycling of unconjugated bilirubin in subjects with Gilbert's syndrome. Annals of hepatology. 2022; 1(1): 40-43 • Bhutani VK, Johnson L, Sivieri EM. Predictive Ability of a Predischarge Hour-specific Serum Bilirubin for Subsequent Significant Hyperbilirubinemia in Healthy Term and Near-term Newborns. Pediatrics. 1999; 103:6-14.

  BACKGROUND

• • Duryea EL, Hawkins JS, McIntire DD, Casey BM, Leveno KJ. A Revised Birth Weight Reference for the United States. Obstetrics & Gynecology. 2014; 124. • Rasul CH, Hasan MA, Yasmin F. Outcome of neonatal hyperbilirubinemia in a tertiary care hospital in bangladesh. The Malaysian journal of medical sciences: MJMS. 2010; 17:40-44. • Johnsen Ø, Eliasson R. Evaluation of a commercially available kit for the colorimetric determination of zinc in human seminal plasma. International Journal of Andrology. 1987; 10:435-440. • Rana N, Mishra S, Bhatnagar S, Paul V, Deorari AK, Agarwal R. Efficacy of Zinc in Reducing Hyperbilirubinemia among At-Risk Neonates: A Randomized, Double-Blind, Placebo-Controlled Trial. The Indian Journal of Pediatrics. 2011; 78:1073-1078. • Patton P, Rachmadi D, Sukadi A. Effect of oral zinc on hyperbilirubinemia in full term neonates. Paediatrica Indonesiana. 2011; 51:107-10. • Faal G, Masjedi HK, Sharifzadeh G, Kiani Z. Efficacy of zinc sulfate on indirect hyperbilirubinemia in premature infants admitted to neonatal intensive care unit: a double-blind, randomized clinical trial. BMC pediatrics. 2020; 20:1-7.

  BACKGROUND

• • Mandlecha TH, Mundada SM, Gire PK, Reddy N, Khaire P, Joshi T, Pawar S. Effect of Oral Zinc Supplementation on Serum Bilirubin Levels in Term Neonates With Hyperbilirubinemia Undergoing Phototherapy: A Double-blind Randomized Controlled Trial. Indian Pediatrics. 2023; 60:991-995. • Elfarargy MS, Al-Ashmawy MG, Abu-Risha SE, Khattab H. Zinc Supplementation in Preterm Neonates with Jaundice: Is it Beneficial?. Endocr Metab Immune Disord Drug Targets. 2021; 21(10):1929-1934. • Mafinezhad S, Bayani G, Bozorgnia Y, Khodaparast M, Jodat S. Effect of oral zinc sulfate on reducing hyperbilirubinemia among newborns under 1800 gram. Journal of North Khorasan University of Medical Sciences. 2016; 7:897-904. • Indrio F, Baldassarre ME, Francavilla R. Will Hyperbilirubinemic Neonates Ever Benefit from Oral Zinc Salt?. Journal of Pediatric Gastroenterology and Nutrition. 2006; 42:118-119.

  BACKGROUND

MeSH Terms

Conditions

Jaundice, Neonatal

Interventions

Zinc Sulfate

Condition Hierarchy (Ancestors)

Hyperbilirubinemia, Neonatal; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperbilirubinemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfates; Sulfuric Acids; Sulfur Acids; Sulfur Compounds; Inorganic Chemicals; Zinc Compounds

Study Officials

• Heba S. Sallam, specialist

  Al-Dalangat Central Hospital, Beheira, Egypt

  PRINCIPAL INVESTIGATOR

• Hala H. Elsaeed, professor

  National liver institute. Menoufia university, Egypt

  STUDY CHAIR

• Mohsen H Hussein, professor

  National liver institute. Menoufia university, Egypt

  STUDY CHAIR

• Hanaa A. El- Alraby

  National liver institute. Menoufia university, Egypt

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Investigators (research staff) and parents of the patients were aware of the treatment
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant professor

Model Details: This randomized clinical trial was carried out on 192 neonates with indirect hyperbilirubinemia, at neonatal intensive care unit (NICU) of Pediatric Department, National Liver Institute (NLI), Menoufia University from (June 2018- June 2019). Research Ethics Committee of NLI approved the study, NLI- Institutional Review Board (IRB) protocol number is (00136/2018). Neonates enrolled in the study were randomly assigned into two groups. Group (1) (zinc and phototherapy group) included 95 neonates receiving phototherapy and oral zinc sulfate with a dose of 5 mg every 12 hours using a calibrated dropper provided with the bottle, during the period of NICU admission on phototherapy. Group (2) (phototherapy group) included 97 neonates receiving phototherapy alone. Both groups receiving phototherapy based on the guidelines of American Academy of Pediatrics for the treatment of neonatal indirect hyperbilirubinemia. Any adverse effect were noted and recorded.

Study Record Dates

• First Submitted: January 10, 2024
• First Posted: January 29, 2024
• Study Start: June 1, 2018
• Primary Completion: June 1, 2019
• Study Completion: January 1, 2020
• Last Updated: January 29, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data will be available after research submission, and for ever
• Access Criteria: journal web sit of publication

Locations

EG (1)