EFFICACY OF MELATONIN IN MANAGEMENT OF HYPOXIC ISCHEMIC ENCEPHALOPATHY (HIE) IN NEONATES

NCT07305350 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: No/779/CH-UCHS
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

To compare the survival rate and improvement in stage of hypoxic ischemic encephalopathy (HIE) at day 7 of treatment in neonates treated with versus without melatonin in addition to standard supportive therapy.

Conditions

Hypoxic Ischaemic Encephalopathy (HIE)

Keywords

Hypoxic ischemic encephalopathy (HIE); Melatonin; Randomized Control Trial

Outcome Measures

Primary Outcomes (1)

• Neonate survival rate

  Role of melatonin will be determined primarily by survival rate in neonates with hypoxic ischemic encephalopathy at 28 days of life.

  28 days of life

Secondary Outcomes (1)

• Improvement in stage of HIE

  Day 1, 3 and 7 of life

Study Arms (2)

Group A

EXPERIMENTAL

55 neonates will be assigned group A in which newborns will be given single 10mg dose of melatonin through nasogastric tube in addition to standard supportive therapy.

Drug: Melatonin

Group B

ACTIVE COMPARATOR

55 neonates will be assigned group B in which patients will be given standard supportive therapy only. Standard supportive therapy included oxygen therapy, intravenous (IV) fluids, intensive monitoring, broad-spectrum antibiotic cover for possible role of infection

Combination Product: intravenous (IV) fluids, intensive monitoring, broad-spectrum antibiotic cover

Interventions

Melatonin DRUG

55 neonates will be assigned group A in which newborns will be given single 10mg dose of melatonin through nasogastric tube in addition to standard supportive therapy.

Group A

intravenous (IV) fluids, intensive monitoring, broad-spectrum antibiotic cover COMBINATION_PRODUCT

55 neonates will be assigned group B in which patients will be given standard supportive therapy only.

Group B

Eligibility Criteria

• Age: 1 Hour+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• All term infants (as per operational definition). Both genders. Presenting with hypoxic ischemic encephalopathy (as per operational definition).

You may not qualify if:

• Drug reactions. Newborns at gestational age \< 36 weeks. Neonates whose mother received general anesthesia. Neonates with congenital malformations. Neonates whose mother received anticonvulsants. Neonates not fulfilling criteria for HIE. Neonatal sepsis, pneumonia or in-born error of metabolism.

Sponsors & Collaborators

• University of Child Health Sciences and Children's Hospital, Lahore: lead

Study Sites (1)

Children Hospital and University of Child Health Sciences, Lahore

Lahore, Punjab Province, 05411, Pakistan

Location

Related Publications (13)

• Siddiqui MA, Butt TK. Role of Intravenous Magnesium Sulphate in Term Neonates with Hypoxic Ischemic Encephalopathy (HIE) in a Low-income Country: A Randomised Clinical Trial. J Coll Physicians Surg Pak. 2021 Jul;31(7):817-820. doi: 10.29271/jcpsp.2021.07.817.

  PMID: 34271782 BACKGROUND

• Ran Y, Ye L, Ding Z, Gao F, Yang S, Fang B, Liu Z, Xi J. Melatonin Protects Against Ischemic Brain Injury by Modulating PI3K/AKT Signaling Pathway via Suppression of PTEN Activity. ASN Neuro. 2021 Jan-Dec;13:17590914211022888. doi: 10.1177/17590914211022888.

  PMID: 34120482 BACKGROUND

• Packer CH, Hersh AR, Sargent JA, Caughey AB. Therapeutic hypothermia in severe hypoxic-ischemic encephalopathy: a cost-effectiveness analysis. J Matern Fetal Neonatal Med. 2022 Mar;35(5):890-897. doi: 10.1080/14767058.2020.1733519. Epub 2020 Mar 10.

  PMID: 32156180 BACKGROUND

• Michniewicz B, Al Saad SR, Karbowski LM, Gadzinowski J, Szymankiewicz M, Szpecht D. Organ Complications of Infants with Hypoxic Ischemic Encephalopathy Before Therapeutic Hypothermia. Ther Hypothermia Temp Manag. 2021 Mar;11(1):58-63. doi: 10.1089/ther.2020.0035. Epub 2020 Nov 5.

  PMID: 33155883 BACKGROUND

• Iqbal N, Younus J, Malik M, Fatima B, Imran A, Maqbool S, Irfan Waheed KA, Haque K. The Neuroprotective Efficacy of Postnatal Magnesium Sulfate in Term or Near-Term Infants With Moderate-to-Severe Birth Asphyxia. Cureus. 2021 Aug 2;13(8):e16826. doi: 10.7759/cureus.16826. eCollection 2021 Aug.

  PMID: 34513419 BACKGROUND

• Go H, Saito Y, Maeda H, Maeda R, Yaginuma K, Ogasawara K, Kashiwabara N, Kawasaki Y, Hosoya M. Serum cytokine profiling in neonates with hypoxic ischemic encephalopathy. J Neonatal Perinatal Med. 2021;14(2):177-182. doi: 10.3233/NPM-200431.

  PMID: 33074195 BACKGROUND

• Florido J, Rodriguez-Santana C, Martinez-Ruiz L, Lopez-Rodriguez A, Acuna-Castroviejo D, Rusanova I, Escames G. Understanding the Mechanism of Action of Melatonin, Which Induces ROS Production in Cancer Cells. Antioxidants (Basel). 2022 Aug 20;11(8):1621. doi: 10.3390/antiox11081621.

  PMID: 36009340 BACKGROUND

• Dolan F, Wintermark P. Updates in Treatment of Hypoxic-Ischemic Encephalopathy. Clin Perinatol. 2025 Jun;52(2):321-343. doi: 10.1016/j.clp.2025.02.010. Epub 2025 Mar 21.

  PMID: 40350214 BACKGROUND

• Cornet MC, Kuzniewicz M, Scheffler A, Forquer H, Hamilton E, Newman TB, Wu YW. Perinatal Hypoxic-Ischemic Encephalopathy: Incidence Over Time Within a Modern US Birth Cohort. Pediatr Neurol. 2023 Dec;149:145-150. doi: 10.1016/j.pediatrneurol.2023.08.037. Epub 2023 Aug 31.

  PMID: 37883841 BACKGROUND

• Chakkarapani E, de Vries LS, Ferriero DM, Gunn AJ. Neonatal encephalopathy and hypoxic-ischemic encephalopathy: the state of the art. Pediatr Res. 2025 Dec;98(7):2444-2458. doi: 10.1038/s41390-025-03986-2. Epub 2025 Mar 24.

  PMID: 40128590 BACKGROUND

• Bobba PS, Malhotra A, Sheth KN, Taylor SN, Ment LR, Payabvash S. Brain injury patterns in hypoxic ischemic encephalopathy of term neonates. J Neuroimaging. 2023 Jan;33(1):79-84. doi: 10.1111/jon.13052. Epub 2022 Sep 26.

  PMID: 36164277 BACKGROUND

• Ahmad QM, Chishti AL, Waseem N. Role of melatonin in management of hypoxic ischaemic encephalopathy in newborns: A randomized control trial. J Pak Med Assoc. 2018 Aug;68(8):1233-1237.

  PMID: 30108392 BACKGROUND

• Ahmed J, Pullattayil S AK, Robertson NJ, More K. Melatonin for neuroprotection in neonatal encephalopathy: A systematic review & meta-analysis of clinical trials. Eur J Paediatr Neurol. 2021 Mar;31:38-45. doi: 10.1016/j.ejpn.2021.02.003. Epub 2021 Feb 11.

  PMID: 33601197 BACKGROUND

MeSH Terms

Conditions

Hypoxia-Ischemia, Brain

Interventions

Melatonin; Fluid Therapy

Condition Hierarchy (Ancestors)

Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypoxia, Brain; Vascular Diseases; Cardiovascular Diseases; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Drug Therapy; Therapeutics

Study Officials

• Muhammad Khalid Masood, MBBS, FCPS

  Children Hospital and University of Child Health Sciences, Lahore

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr Amina Cheema

Model Details: It is a Randomized control trial

Study Record Dates

• First Submitted: December 12, 2025
• First Posted: December 26, 2025
• Study Start: December 10, 2025
• Primary Completion: May 10, 2026
• Study Completion: May 10, 2026
• Last Updated: December 26, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

PA (1)