Although a 2003 clinical trial overwhelmingly found that 17-α-hydroxyprogesterone caproate (17-OHPC) significantly decreases recurrent preterm birth (PTB) and neonatal morbidity, a recently published study in the American Journal of Perinatology found drastically different results. The original study from Meis et al. was shut down early due to large treatment benefit, but the current study suggests that stoppage may have been premature.
The 17-OHCP to Prevent Recurrent Preterm Birth in Singleton Gestations (PROLONG) Study was a multicenter, randomized, controlled, parallel group, double-blind trial at 93 total centers across nine countries. Clinical sites were required to be associated with a hospital that had access to level-3 or greater neonatal intensive care unit (NICU). Participants were limited to women ≥ 18 years with a singleton pregnancy complicated by a singleton SPTB and who were 160/7to 206/7weeks following spontaneous preterm birth (SPTB) or preterm rupture of membranes (PROM). Participants were randomized in a 2:1 ratio to receive either weekly intramuscular (IM) injections of 250 mg of 17-OHPC or an inert oil placebo. The injection treatment was continued until delivery or 36 weeks.
The co-primary outcomes were PTB at < 35 weeks and a neonatal morbidity composite index. The composite included: neonatal death, grade 3 or 4 intraventricular hemorrhage, proven sepsis, necrotizing enterocolitis, respiratory distress syndrome, or bronchopulmonary dysplasia.
The first patient enrolled in the study was randomized on November 12, 2009 and the last study visit was October 8, 2018. A total of 1,708 women were eligible for the study and returned for the randomization visit. Of them, 1,130 were allocated to 17-OHPC and 578 were given placebo. Geographically, 391 women were randomized in the United States and 1,317 women were randomized outside of the country. There were no differences in demographic or clinical characteristics between the study groups. A large majority (87%) of the participants were white, few had > 1 prior SPTB, 89% were married, and 8% smoked.