Ignite Creation Date:
2024-05-06 @ 12:44 AM
Last Modification Date:
2024-10-26 @ 10:54 AM
Study NCT ID:
NCT01646619
Status:
UNKNOWN
Last Update Posted:
2013-04-04
First Post:
2012-07-05
Brief Title:
Efficacy Study of Hypothermia Plus Magnesium SulphateMgSO4 in the Management of Term and Near Term Babies With Hypoxic Ischemic Encephalopathy
Sponsor:
Sajjad Rahman
Organization:
Hamad Medical Corporation
Study Overview
Official Title:
A Multicenter Randomized Controlled Trial of Therapeutic Hypothermia Plus Magnesium Sulphate MgSO4 Versus Therapeutic Hypothermia Plus Placebo in the Management of Term and Near Term Babies With Hypoxic Ischemic Encephalopathy
Status:
UNKNOWN
Status Verified Date:
2013-04
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MagCool
Brief Summary:
The purpose of this study is to assess whether the addition of a drug such as Magnesium sulphate while providing therapeutic hypothermia or cooling to babies who are asphyxiated at birth provides additional benefit to the babies survival and outcome compared to cooling alone
Detailed Description:
Perinatal Asphyxia continues to be a major cause of neonatal mortality and morbidity even in the most technologically advanced and prosperous countries of the world The incidence remains unchanged 1-2 of live births in developed world countries and much higher in developing world countries Perinatal Asphyxia is a multisystem disorder Neonatal brain is the most important organ affected by Asphyxic insult because the resulting neuronal damage is permanent Hypoxic Ischemic Encephalopathy HIE the pathognomonic clinical syndrome of asphyxic neuronal insult occurs in 50-60 of babies with Perinatal Asphyxia Moderate and severe HIE causes significant neonatal mortality and morbidity Among patients with moderate HIE 10-20 die and 30-40 develop neurological deficit whereas 50 of patients with severe HIE die and almost all survivors develop neurological deficits Hence the toll on the society continues to be very high in spite of dramatic improvements in neonatal intact survival particularly in developed world countries
Until recent years the management of HIE was limited to supportive intensive care only because there was no specific treatment available to rescue neurons during HIE However over the last decade therapeutic Hypothermia has emerged as a promising new therapy in reducing neonatal mortality and morbidity due to HIE This is due to improved understanding of the physiology of neuronal damage during asphyxia insult Hypoxic Ischemic Encephalopathy HIE is a dynamic process which evolves over a period of seventy two hours starting from the time of insult Two distinct episodes of neuronal damage occur during this time
1 The immediate primary hypoxic insult followed by a
2 latent period of recovery which lasts for almost six hours
This is followed by a much longer and profound period of secondary neuronal damage due to the release of chemical mediators Therapeutic modalities which can potentially reduce the release of these chemical mediators will provide neuronal rescue Moderate controlled hypothermia 335-345 0C offered during the first 72 hours after the asphyxic insult is one such therapeutic modality which has been the subject of animal studies as well as extensive multicenter trails in human infants over the last two decades
The studies on animal models have not only confirmed the safety of moderate therapeutic hypothermia they have also shown a dramatic neuronal rescue in experimental HIE model of lambs subjected to prolonged therapeutic hypothermia immediately after birth This was followed by pilot RCTs in human infants the outcomes of which were very encouraging However a universal change of practice requires large well designed multicenter trails and Meta analyses
After having established therapeutic hypothermia as a safe and effective modality for neuroprotection in HIE the neonatologists are facing a new question Can the investigators enhance the neuroprotective effect of therapeutic hypothermia by adding other potential neuroprotective agents These potential therapeutic agents include Xenon Erythropoetin Magnisium sulphate Allopurinol opoids Topiramate Inhaled Nitric Oxide iNO N-Acetylcystine Minocycline and Melatonin1317 Due to their different mechanisms of action it is likely that these neuroprotective therapies may add incrementally to the proven beneficial effects of hypothermia Indeed hypothermia may buy additional time for these neuroprotective agents to act within an expanded therapeutic window13 These Hypothermia plus therapies are going to be the subject of many new RCTs worldwide over the next few years
Magnesium Sulphate a potential neuroprotective agent acts by reducing neuronal excitotoxicity MgSO4 has long been used in Obstertrics as a tocolytic agent and has a proven neuroprotective effect in preterm babies born to mothers tocolyzed with MgSO4 A recently conducted RCT in human neonates has compared postnatal magnesium sulfate with placebo in the management of Neonatal HIE This study which did not use hypothermia therapy due to lack of facilities has shown that treatment with MgSO4 improves neurologic outcomes at discharge in term neonates with severe perinatal asphyxia The animal studies done by Knuckleys group has compared a combination of therapeutic hypothermia and MgSO4 with therapeutic hypothermia alone In their rat model MgSO4 alone had a minimal beneficial effect However MgSO4 plus hypothermia had a significant beneficial effect in reducing the size of the post asphyxia infarct This animal focal stroke model provides an intriguing suggestion that hypothermia plus MgSO4 provides an additive neuroprotection No human studies have been done so far to test the difference between therapeutic hypothermia alone and therapeutic hypothermia plus MgSO4 Mag Cool Study Hypothermia plus MgSO4 Vs Hypothermia plus placebo will test this hypothesis
Until recent years the management of HIE was limited to supportive intensive care only because there was no specific treatment available to rescue neurons during HIE However over the last decade therapeutic Hypothermia has emerged as a promising new therapy in reducing neonatal mortality and morbidity due to HIE This is due to improved understanding of the physiology of neuronal damage during asphyxia insult Hypoxic Ischemic Encephalopathy HIE is a dynamic process which evolves over a period of seventy two hours starting from the time of insult Two distinct episodes of neuronal damage occur during this time
1 The immediate primary hypoxic insult followed by a
2 latent period of recovery which lasts for almost six hours
This is followed by a much longer and profound period of secondary neuronal damage due to the release of chemical mediators Therapeutic modalities which can potentially reduce the release of these chemical mediators will provide neuronal rescue Moderate controlled hypothermia 335-345 0C offered during the first 72 hours after the asphyxic insult is one such therapeutic modality which has been the subject of animal studies as well as extensive multicenter trails in human infants over the last two decades
The studies on animal models have not only confirmed the safety of moderate therapeutic hypothermia they have also shown a dramatic neuronal rescue in experimental HIE model of lambs subjected to prolonged therapeutic hypothermia immediately after birth This was followed by pilot RCTs in human infants the outcomes of which were very encouraging However a universal change of practice requires large well designed multicenter trails and Meta analyses
After having established therapeutic hypothermia as a safe and effective modality for neuroprotection in HIE the neonatologists are facing a new question Can the investigators enhance the neuroprotective effect of therapeutic hypothermia by adding other potential neuroprotective agents These potential therapeutic agents include Xenon Erythropoetin Magnisium sulphate Allopurinol opoids Topiramate Inhaled Nitric Oxide iNO N-Acetylcystine Minocycline and Melatonin1317 Due to their different mechanisms of action it is likely that these neuroprotective therapies may add incrementally to the proven beneficial effects of hypothermia Indeed hypothermia may buy additional time for these neuroprotective agents to act within an expanded therapeutic window13 These Hypothermia plus therapies are going to be the subject of many new RCTs worldwide over the next few years
Magnesium Sulphate a potential neuroprotective agent acts by reducing neuronal excitotoxicity MgSO4 has long been used in Obstertrics as a tocolytic agent and has a proven neuroprotective effect in preterm babies born to mothers tocolyzed with MgSO4 A recently conducted RCT in human neonates has compared postnatal magnesium sulfate with placebo in the management of Neonatal HIE This study which did not use hypothermia therapy due to lack of facilities has shown that treatment with MgSO4 improves neurologic outcomes at discharge in term neonates with severe perinatal asphyxia The animal studies done by Knuckleys group has compared a combination of therapeutic hypothermia and MgSO4 with therapeutic hypothermia alone In their rat model MgSO4 alone had a minimal beneficial effect However MgSO4 plus hypothermia had a significant beneficial effect in reducing the size of the post asphyxia infarct This animal focal stroke model provides an intriguing suggestion that hypothermia plus MgSO4 provides an additive neuroprotection No human studies have been done so far to test the difference between therapeutic hypothermia alone and therapeutic hypothermia plus MgSO4 Mag Cool Study Hypothermia plus MgSO4 Vs Hypothermia plus placebo will test this hypothesis
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| HMC-GC1028A | OTHER | Hamad Medical Corporation | None |