Project Description

Background

Every year, an estimated 15 million babies are born preterm, with the majority occurring in the late preterm period (gestation 34 to < 37 weeks). Preterm birth complications are the leading cause of death among children under 5 years of age, accounting for approximately one million deaths in 2015. Approximately 80% of all preterm births occur in South Asia and Sub-Saharan Africa. Preterm neonates face increased risks of short- and long-term respiratory, infectious, and neurological morbidities. Glucocorticoids play a crucial role in fetal development—especially in pulmonary maturation, brain development, and growth. Although Antenatal Corticosteroids (ACS) have long been considered essential in preventing neonatal deaths and severe morbidities due to preterm birth, there remains equipoise regarding their benefits and harms in the late preterm period, particularly in low-resource settings. While WHO guidelines provide clear recommendations for early preterm births, they currently lack definitive guidance for the late preterm period due to insufficient evidence. The ACTION III trial is designed to fill this gap and inform an update of the WHO guidelines on ACS use in the late preterm period.

Objectives

The primary objectives of this trial are:

• To compare the effect of an ACS regimen of dexamethasone phosphate (6mg q12h) for 4 doses or until birth, whichever comes first (Dexa-4x6mg), to placebo on a composite outcome of stillbirth, neonatal death, or use of respiratory support within 72 hours of life when administered to pregnant women at high risk of late preterm birth (34+0 to 36+5 weeks gestation) in low-resource hospitals.
• To compare the effect of an ACS regimen of betamethasone phosphate (2mg q12h) for 4 doses or until birth, whichever comes first (Beta-4x2mg), to placebo on the same composite outcome.
• To compare the effect of the dexamethasone regimen to the betamethasone regimen on the composite outcome.

Method

ACTION III is a parallel group, three-arm, individually randomized, double-blind, placebo-controlled trial. It compares two ACS regimens—dexamethasone phosphate 4x6mg q12h and betamethasone phosphate 4x2mg q12h—administered to women at high risk of preterm birth in the late preterm period. The trial is multi-country and multi-center, implemented in 24 hospitals across Bangladesh, India, Kenya, Nigeria, and Pakistan, with two hospitals in Nigeria; Ile-Ife and Ibadan. Trial activities are facility-based with community follow-up of recruited women and newborns up to 28 days of life.