ACTRN12617001494325 2017.

Study name	The WHO ACTION‐II (Antenatal CorticosTeroids for Improving Outcomes in preterm Newborns) Trial
Methods	Randomised controlled trial Setting: hospitals in Bangladesh, India, Kenya, Nigeria, Pakistan Participants, care givers, outcome assessors and data analysts will all be blinded
Participants	Inclusion criteria Birth planned or expected within 48 hours Gestational age from 34 weeks 0 days to 36 weeks 0 days Women with singleton or multiple pregnancies, where the fetus(es) is(are) alive Women with no clinical signs of severe infection (as per clinical assessment) Women willing and able to provide consent (or if a minor, provides assent and guardian provides consent) Exclusion criteria Intrauterine fetal death Major or lethal congenital fetal anomaly identified Clinical suspicion or evidence of clinical chorioamnionitis, as per obstetric care physician assessment Clinical suspicion or evidence of severe infection, as per obstetric care physician assessment No prior ultrasound‐based estimate of gestational age available and immediate ultrasound examination is not possible Any concurrent or recent (within the past 2 weeks) systemic corticosteroid use during the current pregnancy (outside of trial) Unwilling or unable to provide consent Currently a participant in another clinical trial related to maternal and neonatal health Any other clinical indication where the treating clinician considers corticosteroids to be contraindicated Target sample size: 22,589 women
Interventions	Experimental group: a single course of 6 mg dexamethasone by intramuscular injection, administered every 12 hours, to a total of four (4) doses (time points 0 hours, 12 hours, 24 hours and 36 hours). If the full regimen is completed, the woman would have received a total of 24 mg in divided doses. No repeat course(s) will be used. Control group: Identical placebo (normal saline), administered according to the same regimen as for dexamethasone, with one injection every 12 hours to a total of four doses. Follow‐up of enrolled women and newborns to 28 days postpartum/postnatal
Outcomes	Neonatal death (death of a liveborn within 28 completed days of life) Stillbirth or neonatal death (any death of a fetus (post enrolment), or death of a live birth within 28 completed days of life among all enrolled participants. Possible maternal bacterial infection (occurrence of maternal fever, or clinically suspected or confirmed infection, for which therapeutic antibiotics were used) Stillbirth Early neonatal death Neonatal sepsis Severe intraventricular haemorrhage (sIVH) Neonatal hypoglycaemia Apgar score <7 at 5 minutes Maternal death Maternal fever (greater than or equal to 38.0 C ) Chorioamnionitis Postpartum endometritis Wound infection Non‐obstetric infection Major neonatal resuscitation at birth Timing of breast milk feeding initiation Timing to full enteral feeding Use of oxygen therapy Continuous positive airway pressure (CPAP) ventilation Mechanical ventilation Use of therapeutic antibiotics for 5 or more days Surfactant treatment Length of newborn's hospital stay after birth Admission of newborn to a special newborn care unit Newborn readmission for healthcare at facility Maternal therapeutic antibiotic use Any use of antibiotics in an enrolled participant (maternal) while in facility (prophylactic or therapeutic) Length of total maternal hospitalisation for birth Maternal readmission for healthcare at facility Any maternal referral to another facility Compliance with study allocation Total number of treatment or placebo doses received Time from initiation of first dose until birth Gestational age at birth
Starting date	Registered October 2017 (prospectively registered) Last update: October 2010
Contact information	Dr A. Metin Gulmezoglu gulmezoglum@who.int
Notes	Funding sources: Bill and Melinda Gates Foundation