Mifepristone followed by misoprostol compared to placebo followed by misoprostol as medical treatment for early pregnancy failure (the Triple M Trial): a double-blind placebo-controlled randomized trial

Background Early pregnancy failure (EPF) occurs in > 10 % of pregnancies and worldwide > 20 million women seek treatment for EPF each year. Although medical treatment with misoprostol is widely used already, it is only effective in about 60% of patients. There is still debate whether pre-treatment with mifepristone prior to misoprostol improves the success rate of medical management of EPF.

Methods A multicentre, double-blind, placebo-controlled randomized controlled trial (RCT) was executed at 17 hospitals in the Netherlands. Women with a nonviable pregnancy between 6 and 14 weeks gestation were eligible for inclusion after at least one week expectant management. Participants were randomized in a 1:1 between oral pre-treatment with 600 mg mifepristone or placebo. On day three, and if necessary on day four, participants took two tablets of 200 mcg misoprostol orally, repeated after 4 hours. Group assignment was masked to all involved. The primary outcome was complete evacuation of the uterus (expulsion of gestational sac and endometrial thickness <  15 mm) using only the allocated therapy, 6-8 weeks after treatment.

Findings Inclusions ended after the pre-planned interim-analysis. A total of 351 women were included and randomized (175 to mifepristone and 176 to placebo), and 344 included in the intention-to-treat analysis. Complete evacuation occurred significantly more frequent in the mifepristone group. The frequency of serious adverse events was significantly lower in the mifepristone group.

Interpretation Pre-treatment with mifepristone prior to misoprostol significantly improves the complete evacuation rate in EPF, with a number needed to treat (NNT) of 4.9.

Publication History

Article published online:
07 October 2020