Neuroprotective Efficacy of Postnatal Magnesium Sulphate in Term Infants With Birth Asphyxia

Study Overview
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Brief Summary
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Birth/Perinatal asphyxia in Pakistan continues to be a leading cause of neonatal mortality and morbidity. It is estimated that around 80 to 120,000 neonates either suffer from or die from birth/perinatal asphyxia every year. In addition to the large number of deaths a larger number of babies who survive suffer from neuro-developmental disorders adding to the health burden to the society and the nation. To date other than prevention (which requires global efforts to improve maternal education and health care) the therapies available to treat infants who have suffered from birth asphyxia have been either technically too complex or extremely expensive.

Detailed Description
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Birth/Perinatal asphyxia in Pakistan continues to be a leading cause of neonatal mortality and morbidity. It is estimated that around 80 to 120,000 neonates either suffer from or die from birth/perinatal asphyxia every year. In addition to the large number of deaths a larger number of babies who survive suffer from neuro-developmental disorders adding to the health burden to the society and the nation. To date other than prevention (which requires global efforts to improve maternal education and health care) the therapies available to treat infants who have suffered from birth asphyxia have been either technically too complex or extremely expensive. Recent evidence from animal studies and small human studies it has become clear that giving Magnesium Sulphate to term or nearterm babies with moderate to severe birth/perinatal asphyxia reduces both mortality and morbidity. Magnesium Sulphate as a drug has been in clinical use for decades; its pharmacokinetics, safety profile and mode of action are well known. It is cheap and readily available in Pakistan thus providing an opportunity to confirm or refute the efficacy of Magnesium Sulphate in birth/perinatal asphyxia. With this in mind the following pragmatic study has been designed using the current practices and available resources:

Official Title
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A Multicentre Double Blind Trial of the Neuroprotective Efficacy of Postnatal Magnesium Sulphate in Term/Near Term Infants With Moderate to Severe Birth Asphyxia

Conditions
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Birth Asphyxia

Intervention / Treatment
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* Drug: Magnesium sulfate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Term and near term infants (≥35 weeks gestation) with moderate to severe birth asphyxia Age at admission < 24 hours Exclusion Criteria: Babies who could not be given first injection before 24 hours of age Infants with major congenital malformations, sepsis, congenital heart defects, Intracranial hemorrhage and surgical problems Babies received intubated in emergency Babies receiving therapeutic hypothermia Infants with disorders of metabolism Infants in whom cause other than asphyxia is established as the reason for not initiating or sustaining breathing at birth.

Ages Eligible for Study
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Minimum Age: 1 Hour
Maximum Age: 24 Hours

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: All babies with moderate or severe Hypoxic Ischemic Encephalopathy fulfilling the inclusion criteria will be randomized to receive either the standard treatment (oxygen and fluid therapy along with anticonvulsants if required) plus 3.0 ml/kg of 10% dextrose water given over 30 minutes, three dose given 24 hours apart or to receive standard treatment PLUS three doses of Magnesium Sulphate infusion given over 30 minutes at 250 mg/kg per dose given 24 hours apart. The volume of infusion shall be adjusted with 10% dextrose water to make it
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: intervention group<br>All babies with moderate or severe Hypoxic Ischemic Encephalopathy fulfilling the inclusion criteria will be randomized to receive either the standard treatment (oxygen and fluid therapy along with anticonvulsants if required) plus 3.0 ml/kg of 10% dextrose water given over 30 minutes, three dose given 24 hours apart or to receive standard treatment PLUS three doses of Magnesium Sulphate infusion given over 30 minutes at 250 mg/kg per dose given 24 hours apart. The volume of infusion shall be adjusted with 10% dextrose water to make it up to 3.0 ml. The resulting reconstituted solution for intravenous infusion shall be 8.3% Magnesium Sulphate delivered over 30 minutes at a rate of 0.1 ml/kg/minute i.e. 8.3 mg/kg/minute. The treatment should be started as soon after birth as possible and not later than 24 hours of life. The babies who meet the exclusion criteria will not be continued into the study. | Drug: Magnesium sulfate<br>* All babies with moderate or severe Hypoxic Ischemic Encephalopathy fulfilling the inclusion criteria will be randomized to receive either the standard treatment (oxygen and fluid therapy along with anticonvulsants if required) plus 3.0 ml/kg of 10% dextrose water given over 30 minutes, three dose given 24 hours apart or to receive standard treatment PLUS three doses of Magnesium Sulphate infusion given over 30 minutes at 250 mg/kg per dose given 24 hours apart. The volume of infusion shall be adjusted with 10% dextrose water to make it up to 3.0 ml. The resulting reconstituted solution for intravenous infusion shall be 8.3% Magnesium Sulphate delivered over 30 minutes at a rate of 0.1 ml/kg/minute i.e. 8.3 mg/kg/minute. The treatment should be started as soon after birth as possible and not later than 24 hours of life. The babies who meet the exclusion criteria will not be continued into the study.<br>* Other names: neuroprotective agent;|
| No Intervention: non intervention group<br>All babies with moderate or severe Hypoxic Ischemic Encephalopathy fulfilling the inclusion criteria will be randomized to receive either the standard treatment (oxygen and fluid therapy along with anticonvulsants if required) plus 3.0 ml/kg of 10% dextrose water given over 30 minutes, three dose given 24 hours apart or to receive standard treatment PLUS three doses of Magnesium Sulphate infusion given over 30 minutes at 250 mg/kg per dose given 24 hours apart. The volume of infusion shall be adjusted with 10% dextrose water to make it up to 3.0 ml. The resulting reconstituted solution for intravenous infusion shall be 8.3% Magnesium Sulphate delivered over 30 minutes at a rate of 0.1 ml/kg/minute i.e. 8.3 mg/kg/minute. The treatment should be started as soon after birth as possible and not later than 24 hours of life. The babies who meet the exclusion criteria will not be continued into the study. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of participants died (receiving mgso4) | Mortality between the two groups (Standard management vs Magnesium Sulphate treated group). Further analyzed by the stage of asphyxia | 6 hours | 
| number of participants diednumber (difference in time of administration) | Mortality between the two groups (Standard management vs Magnesium Sulphate treated group) in those where magnesium sulphate was given within six hours of birth and those given later than six hours of birth. | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of seizure episode | Frequency of seizures in the two groups and number of days to achieve seizure control. | 6 hours | 
| days in achieving full enteral feed | Number of days to achieve oral feed. | 1 month | 
| assessment of neurodevelopmental damage | Neurodevelopmental disability in survivors at 18 months of age as assessed by a developmental pediatrician blinded to the study groups using one standard developmental screening method in all babies | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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birth asphyxia, magnesium sulphate, term infants