A multi-country, multicenter, two-arm, parallel, double-blind, placebo-controlled, randomized trial of antenatal corticosteroids for women at risk of imminent birth in the early preterm period in hospitals in low-resource countries to improve newborn outcomes (ACTION-I Trial).
The primary objectives of this study were (1) to compare the effect of dexamethasone to placebo on stillbirth and neonatal survival when given to pregnant women at risk of imminent preterm birth in hospitals in low resource countries; (2) to compare the effect of dexamethasone to placebo on possible maternal bacterial infections when given to pregnant women at risk of imminent preterm birth in hospitals in low resource countries; (3) to compare the effect of dexamethasone to placebo on severe neonatal respiratory distress in hospitals in low resource countries.
It was a parallel, two-arm, double-blind, randomized, placebo-controlled trial of antenatal corticosteroids for women at risk of imminent preterm birth. This trial was part of a larger multi-country, multi-center study led by WHO in Bangladesh, India, Kenya, Nigeria, and Pakistan, where the ACS treatment criteria can reasonably be met. In Bangladesh trial activities took place in six hospitals (Institute of Mother and Child Health; Centre for Woman and Child Health; Enam Medical College Hospital; Sylhet MAG Osmani Medical College Hospital; Jalalabad Ragib-Rabeya Medical College Hospital and Sylhet Women’s Medical College Hospital).
Pregnant women with confirmed live fetuses from 26 weeks to 33 weeks 0 days of gestation with imminent preterm birth were eligible for inclusion. The study participants were randomly assigned in a 1:1 ratio and received a course of 6 mg intramuscular dexamethasone or identical placebo administered every 12 hours, for a maximum of four doses, or until hospital discharge or birth. Trial participants (women and their babies) were followed up from randomization to 28 completed days after birth.
In ACTION-I trial, a total of 2852 women (and their 3070 fetuses) were randomized from 29 hospitals across Bangladesh, India, Kenya, Nigeria, and Pakistan. The trial was stopped for benefit at the second interim analysis. The trial results revealed that the use of dexamethasone resulted in significantly lower risks of neonatal death (relative risk, 0.84; 95% confidence interval [CI], 0.72 to 0.97; P=0.03) and stillbirth or neonatal death (relative risk, 0.88; 95% CI, 0.78 to 0.99; P=0.04) than the use of placebo, without an increase in the incidence of possible maternal bacterial infection (relative risk, 0.76; 95% CI, 0.56 to 1.03).
The ACTION-I trial protocol paper has been published in 2019 (Bahl et al., 2019) and the trial result has been published in 2020 (Oladapo et al., 2020).