Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jan 6:32:100716.
doi: 10.1016/j.eclinm.2020.100716. eCollection 2021 Feb.

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

Charlotte Hamel  1   2 , Sjors Coppus  3 , Joyce van den Berg  4 , Esther Hink  2 , Jacoba van Seeters  5 , Paul van Kesteren  6 , Ashley Merién  7 , Bas Torrenga  8 , Rafli van de Laar  9 , Josien Terwisscha van Scheltinga  10 , Ingrid Gaugler-Senden  11 , Peppino Graziosi  12 , Minouche van Rumste  13 , Ewka Nelissen  14 , Frank Vandenbussche  2   15 , Marcus Snijders  1
Affiliations

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

Charlotte Hamel et al. EClinicalMedicine. .

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.

Keywords: Early pregnancy loss; Mifepristone; Misoprostol.

PubMed Disclaimer

Conflict of interest statement

Dr. Hamel reports grants from Healthcare Insurers Innovation Foundation, during the conduct of the study; meant to cover costs of performing the trial, no involvement in any other aspect of the trial such as study design, data gathering/analysis, manuscript preparation. All other authors have nothing to declare.

Figures

Fig. 1:
Fig. 1
trial profile Legend: -----> = included in intention-to-treat analysis → = excluded from intention-to-treat analysis.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Neilson J.P., Gyte G.M.L., Hickey M., Vazquez J.C., Dou L. John Wiley & Sons, Ltd; Chichester, UK: 2009. Medical treatments for incomplete miscarriage (less than 24 weeks) - PMC - PubMed
    1. NICE guideline Ectopic pregnancy and miscarriage: diagnosis and initial management. Natl Inst Heal Care Excell. 2019 https://www.nice.org.uk/guidance/ng126/chapter/Recommendations#symptoms-...
    1. Ammon Avalos L., Galindo C., Li D.K. A systematic review to calculate background miscarriage rates using life table analysis. Birth Defects Res Part A - Clin Mol Teratol. 2012;94:417–423. - PubMed
    1. Buck Louis G.M., Sapra K.J., Schisterman E.F. Lifestyle and pregnancy loss in a contemporary cohort of women recruited before conception: the LIFE Study. Fertil Steril. 2016;106:180–188. - PMC - PubMed
    1. https://data.guttmacher.org/. 2020.

Associated data

LinkOut - more resources