Hypothermia Enhanced by Magnesium Sulphate

NCT02499393 | Completed Phase 2

• 1 other identifier: PolishMMHRI
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

New 2010 neonatal resuscitation guidelines state that offering therapeutic hypothermia (TH) should be a standard of care in managing neonates with perinatal hypoxic - ischemic insult and present with signs of moderate and/or severe hypoxic - ischemic encephalopathy (HIE) . Despite the evidence from several randomized control trial (RCT) proving its effectiveness, its effect is perceived insufficient or only modest. Thus today's research efforts are directed toward finding the new possibilities of enhancing the effects of hypothermia. List of agents with potential neuroprotective properties includes: erythropoetin, melatonin, topiramate, morphine, xenon, MgSO4. Given investigators previous experiences with preterm neonates exposed to MgSO4 prenatally or administered this drug after birth because of perinatal asphyxia, the investigators designed the trial which would evaluate the possibility of increasing the TH effect by combining this method with MgSO4. Until now there are several published studies evaluating the effectiveness of MgSO4 in the group of asphyxiated neonates, including one RCT. However, all of these studies were conducted before the era of TH Furthermore, irrespective of the potential benefits, safety of using MgSO4 during TH in the group of term neonates was not studied. It is particularly important in the light of the results presented by Mittendorf et.al. They studied the effects of prenatal aggressive treatment with MgSO4 on the outcome of preterm neonates showed that patients exposed to high doses of MgSO4 were at higher risk of severe intracranial bleeding. Other side effects of high serum magnesium levels are: vasodilatation, hypotension, cardiac arrhythmias, coagulopathy, and gastrointestinal disturbances. MgSO4 is a very attractive neuroprotective option,also because of its easy availability. Drug can be administered in the birth hospital while neonate is being prepared for the transport to TH center. Timing of the intervention is very important for neonates suffering from perinatal asphyxia. Both TH and administration of potentially neuroprotective drug should be started during "therapeutic window". It is the initial potentially reversible phase of hypoxic insult lasting about 6 hours. If the long-term follow up shows that MgSO4 has an additive neuroprotective effect and no significant side effects in the group of asphyxiated neonates treated with TH this relatively simple and not expensive intervention may be introduced into clinical practice

Conditions

Perinatal Anoxic-ischemic Brain Injury

Keywords

newborn; therapeutic hypothermia; magnesium sulphate

Outcome Measures

Primary Outcomes (1)

• Death

  until discharge (participants will be followed for the duration of hospital stay @ hypothermia center, an expected up to 4 weeks

Secondary Outcomes (2)

• Neurological status

  1-7 DOL

• Neurological status

  24 months

Study Arms (2)

TH+MgSO4

EXPERIMENTAL

Therapeutic hypothermia plus magnesium sulphate intravenous infusion Neonates who were randomized to the study group (TH+MgSO4) received three 250 mg/kg doses of magnesium sulfate given as one - hour continuous infusion spaced 24 hours apart on three consecutive days. 20% Magnesium Sulfuricum (Polpharma), 2 g /10 ml were used.

Drug: Magnesium Sulfate

TH- therapeutic hypothermia

NO INTERVENTION

therapeutic hypothermia without magnesium sulphate

Interventions

Magnesium Sulfate DRUG

intravenous infusion of magnesium sulphate

Also known as: Magnesii Sulfurici 20% Polpharma

TH+MgSO4

Eligibility Criteria

• Age: 1 Hour - 6 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Group A Infants \> 36.0 weeks gestation\* with at least ONE of the following: \* for gestational age also use clinical assessment
• Apgar score of less than or equal to ≤5 at 10 (ten) minutes after birth
• continued need for resuscitation, including endotracheal or mask ventilation, at 10min after birth
• acidosis defined as either umbilical cord pH or any arterial, venous or capillary pH within 60 min of birth less than (\<) pH 7.00
• base deficit greater than or equal to (≥) 16 mmol/L in umbilical cord blood sample or any blood sample within 60 minutes of birth (arterial or venous blood)
• Group B Newborn with moderate or severe encephalopathy with varying states of consciousness: lethargy, stupor, or coma and
• One or more of below:
• hypotonia
• abnormal reflexes : oculomotor / pupillary
• suck: weak / absent
• clinical seizures - clinically confirmed
• Group C integrated electroencephalogram (aEEG / CFM) (lasting at least 20 minutes), which indicates either a moderate / serious abnormalities in the background activity aEEG (a score of 2 or 3) or convulsions attacks.

You may not qualify if:

• major congenital maformation
• extremely poor prognosis : Apgar score 0 @ 15 minutes of life

Sponsors & Collaborators

• Polish Mother Memorial Hospital Research Institute: lead
• Poznan University of Medical Sciences: collaborator

Study Sites (1)

Polish Mother Memorial Hospital - Research Instutiute

Lodz, 93-338, Poland

Location

Related Publications (2)

• Merchant N, Azzopardi D. Early predictors of outcome in infants treated with hypothermia for hypoxic-ischaemic encephalopathy. Dev Med Child Neurol. 2015 Apr;57 Suppl 3:8-16. doi: 10.1111/dmcn.12726.

  PMID: 25800487 BACKGROUND

• Gulczynska EM, Gadzinowski J, Kesiak M, Sobolewska B, Caputa J, Maczko A, Walas W, Cedrowska-Adamus W, Talar T. Therapeutic hypothermia in asphyxiated newborns: selective head cooling vs. whole body cooling - comparison of short term outcomes. Ginekol Pol. 2019;90(7):403-410. doi: 10.5603/GP.2019.0069.

  PMID: 31392710 DERIVED

MeSH Terms

Interventions

Magnesium Sulfate

Intervention Hierarchy (Ancestors)

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

Study Officials

• Ewa Gulczynska, MD PhD

  Polish Mother Memorial Hospital Research Instutute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2015
• First Posted: July 16, 2015
• Study Start: April 1, 2010
• Primary Completion: April 1, 2013
• Study Completion: December 1, 2014
• Last Updated: July 16, 2015

Record last verified: 2015-07

Locations

PL (1)