A randomized, double-masked trial of prophylactic indomethacin tocolysis versus placebo in women with premature rupture of membranes.

Preterm premature rupture of membranes (PPROM) complicates 3% of pregnancies and frequently results in preterm birth, often within 48 hours of membrane rupture. Our objective was to determine if subjects with PPROM between 24 and 31 6 / 7 weeks' gestation benefit from a 48-hour course of prophylactic indomethacin tocolysis. This was a double-masked randomized controlled trial. Subjects with PPROM between 24 and 31 6 / 7 weeks' gestation were randomized to receive indomethacin or placebo for 48 hours in addition to corticosteroids and latency antibiotics. The primary outcome of the study was delivery within 48 hours. Maternal and neonatal outcomes were also compared. This study was concluded prematurely due to slow accrual after a total of 50 subjects were enrolled. A total of 23/25 (92%) subjects in the indomethacin group remained pregnant beyond 48 hours compared with 20/22 (90.9%) in the placebo group (relative risk, 1.01; 95% confidence interval, 0.84 to 1.21). The latency period medians and interquartile ranges were similar between the two groups [indomethacin 193 (92 to 376.5) hours versus placebo 199 (77.5 to 459) hours, P = 0.91], and no differences were noted in any maternal or neonatal secondary outcomes. This limited study demonstrates no benefit with the use of prophylactic indomethacin tocolysis for women with PPROM.