Mifepristone followed by misoprostol compared with placebo followed by misoprostol as medical treatment for early pregnancy loss (the Triple M trial): A double-blind placebo-controlled randomised trial

Abstract

Background Worldwide, millions of women seek treatment for early pregnancy loss (EPL) annually. Medical management with misoprostol is widely used, but only effective 60% of the time. Pre-treatment with mifepristone prior to misoprostol might improve the success rate of medical management. Methods This was a multi-centre, double-blind, placebo-controlled randomised trial in 17 Dutch hospitals. Women with a non-viable pregnancy between 6 and 14 weeks of gestation were eligible for inclusion after at least one week of expectant management. Participants were randomised (1:1) between oral mifepristone 600 mg or an oral placebo tablet. Participants took 400 μg misoprostol orally, repeated after four hours on day two and, if necessary, day three. Primary outcome was expulsion of gestational sac and endometrial thickness <15 mm after 6–8 weeks. Analyses were done according to intention-to-treat principles. This trial is registered with ClinicalTrials.gov, NCT03212352. Findings Between June 28th 2018 and January 8th 2020, 175 women were randomised to mifepristone and 176 to placebo, including 344 in the intention-to-treat analysis. In the mifepristone group 136 (79•1%) of 172 participants reached complete evacuation compared to 101 (58•7%) of 172 participants in the placebo group ( p <0•0001, RR 1•35, 95% CI 1•16–1•56). Incidence of serious adverse events was significantly lower in the mifepristone group with 24 (14%) patients affected versus 55 (32%) in the placebo group ( p = 0•0005) (Table 3). Interpretation Pre-treatment with mifepristone prior to misoprostol was more effective than misoprostol alone in managing EPL. Funding Healthcare Insurers Innovation Foundation, Radboud University Medical Centre, Canisius Wilhelmina Hospital.

Economic evaluation of a randomized controlled trial comparing mifepristone and misoprostol with misoprostol alone in the treatment of early pregnancy loss

“…Recently, whether or not preceded by expectant management, the sequential combination of mifepristone and misoprostol has been shown to be more successful in reaching complete expulsion than misoprostol alone in case of EPL as proven by both our and other research groups [ 16 – 18 ].…”

“…This economic evaluation was performed alongside the Triple M Trial, a nationwide multicentre double-blinded placebo-controlled RCT conducted in 17 Dutch hospitals [ 16 ]. A CONSORT checklist and further details about study design, sample size calculation, study procedures and outcome have been described previously [ 19 ].…”

Prospective open-label non-inferiority randomised controlled trial comparing letrozole and mifepristone pretreatment in medical management of first trimester missed miscarriage: study protocol

“…The reported complete abortion rate of pretreatment with mifepristone followed by misoprostol for the medical management of first trimester missed miscarriage in previous clinical trials has ranged from 79% to 87%, and that of misoprostol alone ranged from 58% to 76%. [17][18][19][20][21][22][23] As access to mifepristone is restricted in some countries, and some patients may have contraindications to the use of mifepristone, it is important to find a replacement for mifepristone for medical treatment of missed miscarriage. 24 We propose that letrozole may be a good alternative.…”

Utility and Limitations of Human Chorionic Gonadotropin Levels for Remote Follow-up After Medical Management of Early Pregnancy Loss

“…M ifepristone pretreatment for medical management of early pregnancy loss improves efficacy compared with misoprostol alone. 1,2 Ultrasonography is often used to confirm treatment completion, although the American College of Obstetricians and Gynecologists acknowledges the role of serial serum human chorionic gonadotropin (hCG) measurements when ultrasonography is unavailable. 3 However, guidance regarding schedule and interpretation of serum hCG measurements to confirm completion is not established.…”