Investigating the effect of melatonin in pro-oxidant antioxidant balance of neonates with hypoxic ischemic encephalopathy: A Randomized Parallel Clinical Trial

determine the effect of melatonin in pro-oxidant antioxidant balance of neonates with hypoxic ischemic encephalopathy

Two arm (intervention and control) Superiority, parallel group randomized (block) with Allocation Concealment trial with blinded care and outcome assessment on 70 infant

This clinical trial will be conducted on infants with hypoxic-ischemic encephalopathy hospitalized in the Mashhad University of Medical Sciences hospitals. After obtaining informed consent from the mothers and completing the informed consent form, infants with a gestational age of more than 32 weeks will be examined.

Criteria for individuals' entry into the study: Infants with a gestational age of 32 weeks or more and a definitive diagnosis of hypoxic-ischemic encephalopathy, which includes at least two of the following: Identifiable intrapartum events (placental abruption, uterine rupture, umbilical cord prolapse) accompanied by intrapartum monitoring disorders, intrapartum fever, or difficult birth. Umbilical cord pH less than 7 or blood pH less than 7.2 in the blood sample within the first hour of birth. BE > -12 in the blood sample within the first hour of birth or umbilical cord. Criteria for exiting the study: Congenital malformations Congenital infections Chorioamnionitis Encephalopathy due to genetic disease Encephalopathy due to metabolic diseases Hyperbilirubinemia encephalopathy

In both the intervention and control groups, infants receive MgSO4 at a rate of 250 mg/kg/day with a one-hour infusion and blood pressure control in the first hour, the second day, and the third day. In the intervention group, infants receive 10 mg/kg/daily of oral melatonin for 5 days.

Level of consciousness, duration of feeding (days), hospitalization (days), need for oxygen (days), number of seizures.

In the upcoming clinical trial, we will utilize block randomization to ensure a balanced allocation between the intervention and control groups. A computer algorithm from the website sealedenvelope.com will generate blocks of a predetermined size (e.g., 4 or 6). Within each block, an equal number of participants will be allocated to both the intervention and control groups. Sealed, numbered envelopes will be used for this purpose. Instead of containing a drug or placebo, each envelope will simply have a label indicating the group—either "Control" or "Intervention"—to which the participant is to be allocated. These envelopes will be distributed to participants based on the block randomization algorithm generated by sealedenvelope.com. An independent team separate from the principal investigators will manage this process to ensure that the randomization is executed accurately and without bias.

The first layer of blinding occurs in the group of participants in such a way that after obtaining informed consent from the parents, no information regarding the therapeutic process of the infant will be provided to them. Given that the infants are kept in the NICU and away from their parents, medication will be administered at times when the parents are not present. The second layer pertains to the outcome evaluator, who will only have access to the names of the participants and will have no information regarding the patient's medication card. Finally, the collected data from both study groups A and B will be delivered to the analyst, who will have no information regarding the allocation of titles A and B to the intervention and control groups.

IPD collected for the primary outcome measure only

starting 6 months after publication

available for people working in academic institutions

upon reasonable request from corresponding author

Boskabadih@mums.ac.ir

If there is a need for the data for another research project, access to the data is possible, provided that the intellectual rights of the authors, the financial provider, and the rights of the project are respected.