Magnesium sulphate at 30 to 34 weeks' gestational age: neuroprotection trial (MAGENTA) -study protocol

Abstract

BACKGROUND: Magnesium sulphate is currently recommended for neuroprotection of preterm infants for women at risk of preterm birth at less than 30 weeks’ gestation, based on high quality evidence of benefit. However there remains uncertainty as to whether these benefits apply at higher gestational ages. The aim of this randomised controlled trial is to assess whether giving magnesium sulphate compared with placebo to women immediately prior to preterm birth between 30 and 34 weeks’ gestation reduces the risk of death or cerebral palsy in their children at two years’ corrected age. METHODS/DESIGN: DESIGN: Randomised, multicentre, placebo controlled trial. INCLUSION CRITERIA: Women, giving informed consent, at risk of preterm birth between 30 to 34 weeks’ gestation, where birth is planned or definitely expected within 24 hours, with a singleton or twin pregnancy and no contraindications to the use of magnesium sulphate. TRIAL ENTRY & RANDOMISATION: Eligible women will be randomly allocated to receive either magnesium sulphate or placebo. TREATMENT GROUPS: Women in the magnesium sulphate group will be administered 50 ml of a 100 ml infusion bag containing 8 g magnesium sulphate heptahydrate [16 mmol magnesium ions]. Women in the placebo group will be administered 50 ml of a 100 ml infusion bag containing isotonic sodium chloride solution (0.9%). Both treatments will be administered through a dedicated IV infusion line over 30 minutes. PRIMARY STUDY OUTCOME: Death or cerebral palsy measured in children at two years’ corrected age. SAMPLE SIZE: 1676 children are required to detect a decrease in the combined outcome of death or cerebral palsy, from 9.6% with placebo to 5.4% with magnesium sulphate (two-sided alpha 0.05, 80% power, 5% loss to follow up, design effect 1.2). DISCUSSION: Given the magnitude of the protective effect in the systematic review, the ongoing uncertainty about benefits at later gestational ages, the serious health and cost consequences of cerebral palsy for the child, family and society, a trial of magnesium sulphate for women at risk of preterm birth between 30 to 34 weeks’ gestation is both important and relevant for clinical practice globally. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry - ACTRN12611000491965