oa Preliminary safety results of Mag Cool 2 study: A randomized controlled trial

Objective To determine the safety of a combination of Magnesium Sulphate and Therapeutic Hypothermia in the management of term and near term newborns with moderate to severe Hypoxic Ischemic Encephalopathy Introduction The neuroprotective research in Hypoxic Ischemic Encephalopthay (HIE) is currently testing Hypothermia plus therapies. The Mag Cool Study aims to test the safety and efficacy of Therapeutic Hypothermia plus Magnesium Sulphate. The current poster presents the preliminary safety results which were presented in the First DSMB meeting of the Trial. Methods Study design: Multicenter, Prospective, Randomized, double blind, placebo controlled trial. Study Duration: June 2012 to December 2013. Funding: HMC Internal Research Grants Competition Qatar (Grant # GC 1028A). IRB Approval: Approved by the IRB of all participating centers. Randomization: Babies were randomized, using a web based randomization system provided by Sealed envelopes Inc. London UK, to Arm A (Magnesium Sulphate 250mg/k/dose for three doses at 24 hours interval or Arm B (an equivalent volume of normal saline as placebo) to be administered as soon as possible after birth; preferably within six hours of birth. Method: Term and near term babies (≥35 completed weeks of gestation) with evidence of moderate to severe Hypoxic Ischemic encephalopathy using Inclusion and Exclusion criteria. All babies were provided standard intensive care plus hypothermia therapy as soon after birth as possible, using either a total body cooling machine or head cooling machine to maintain a rectal temperature of 33.50 C for a period of 72 hours followed by an eight hours period of gradual rewarming to normal body temperature and another 16 hours of observation (total duration 96 hours). Safety outcome measures: Death or severe adverse events during the 96 hours of treatment Analysis SPSS Version 20 was used. Univariate analysis using cross tabulations of Intervention (MgSO4) and Control arms with outcome measures was done. Chi-square test and Fischer Exact test was used. A p-value of <0.05 was taken as significant. Results A total of 34 patients were enrolled in the safety study from 26 May 2012 till 31st April 2013. There were 18 patients in Arm A and 16 in Arm B. Therapeutic hypothermia was successfully maintained between 33.5 and 34.50 C as per standard protocol in all patients except one in which hypothermia was terminated at 62 hours of age due to persistent sinus bradycardia. All 34 patients received intensive care including endotracheal intubation and ventilation Conclusion The combined use of therapeutic hypothermia and MgSO4 appears to be safe particularly with respect to maintaining blood pressure and coagulopathy. Long term survival and neurodevelopmental outcomes remain to be evaluated. Participating Centers and Patients Contributed: Hamad Medical Corporation Qatar, Zekai Tahir Burak Hospital Turkey, Al Rayyan Hospital Riyadh KSA, Mansoura University Children's Hospital Egypt, University Malaya Medical Center Kuala Lumpur Malaysia, Tawam Hospital UAE