Abstract
Background: The anti-progesterone drug mifepristone and the prostaglandin misoprostol can be used to treat missed miscarriage. However, it is unclear whether a combination of mifepristone and misoprostol is more effective than administering misoprostol alone. We investigated whether treatment with mifepristone plus misoprostol would result in a higher rate of completion of missed miscarriage compared with misoprostol alone.
Methods: MifeMiso was a multicentre, double-blind, placebo-controlled, randomised trial in 28 UK hospitals. Women were eligible for enrolment if they were aged 16 years and older, diagnosed with a missed miscarriage by pelvic ultrasound scan in the first 14 weeks of pregnancy, chose to have medical management of miscarriage, and were willing and able to give informed consent. Participants were randomly assigned (1:1) to a single dose of oral mifepristone 200 mg or an oral placebo tablet, both followed by a single dose of vaginal, oral, or sublingual misoprostol 800 μg 2 days later. Randomisation was managed via a secure web-based randomisation program, with minimisation to balance study group assignments according to maternal age (<30 years vs ≥30 years), body-mass index (<35 kg/m 2 vs ≥35 kg/m 2), previous parity (nulliparous women vs parous women), gestational age (<70 days vs ≥70 days), amount of bleeding (Pictorial Blood Assessment Chart score; ≤2 vs ≥3), and randomising centre. Participants, clinicians, pharmacists, trial nurses, and midwives were masked to study group assignment throughout the trial. The primary outcome was failure to spontaneously pass the gestational sac within 7 days after random assignment. Primary analyses were done according to intention-to-treat principles. The trial is registered with the ISRCTN registry, ISRCTN17405024.
Findings: Between Oct 3, 2017, and July 22, 2019, 2595 women were identified as being eligible for the MifeMiso trial. 711 women were randomly assigned to receive either mifepristone and misoprostol (357 women) or placebo and misoprostol (354 women). 696 (98%) of 711 women had available data for the primary outcome. 59 (17%) of 348 women in the mifepristone plus misoprostol group did not pass the gestational sac spontaneously within 7 days versus 82 (24%) of 348 women in the placebo plus misoprostol group (risk ratio [RR] 0·73, 95% CI 0·54–0·99; p=0·043). 62 (17%) of 355 women in the mifepristone plus misoprostol group required surgical intervention to complete the miscarriage versus 87 (25%) of 353 women in the placebo plus misoprostol group (0·71, 0·53–0·95; p=0·021). We found no difference in incidence of adverse events between the study groups.
Interpretation: Treatment with mifepristone plus misoprostol was more effective than misoprostol alone in the management of missed miscarriage. Women with missed miscarriage should be offered mifepristone pretreatment before misoprostol to increase the chance of successful miscarriage management, while reducing the need for miscarriage surgery.
Funding: UK National Institute for Health Research Health Technology Assessment Programme.
| Original language | English |
|---|---|
| Pages (from-to) | 770-778 |
| Number of pages | 9 |
| Journal | The Lancet |
| Volume | 396 |
| Issue number | 10253 |
| Early online date | 24 Aug 2020 |
| DOIs | |
| Publication status | Published - 12 Sept 2020 |
Bibliographical note
Funding Information:AWH reports serving as a consultant for and receiving personal fees from AbbVie, Roche Diagnostics, Ferring, and Nordic Pharma and has received research support grants from the Medical Research Council, National Institute for Health Research, Chief Scientist's Office, Wellbeing of Women, Roche Diagnostics, AstraZeneca, and Ferring, outside the submitted work. All other authors declare no competing interests.
Funding Information:
This report presents independent research commissioned by the National Institute for Health Research (NIHR). A final report of data collected in this study will be published in the NIHR Journals Library . The views expressed in this Article are those of the author(s) and not necessarily those of the UK National Health Service, the NIHR, or the UK Department of Health and Social Care. This project was funded by the NIHR Health Technology Assessment programme (15/160/02). The project was also supported by the Tommy's Charity, whose funding supports the UK National Miscarriage Research Network. We thank all the women who participated in this study; the following investigators for supervising recruitment and randomisation at the study centres: Amna Ahmed, Kalsang Bhatia, Cecilia Bottomley, Ying Cheong, Meena Choudhary, Shilpa Deb, Sangeetha Devarajan, Pratima Gupta, Judith Hamilton, Ismail Hassan, Frances Hodge, Andrew Horne, Feras Izzat, Yadava Jeve, Chitra Kumar, Jane Mears, Faizah Mukri, Natalie Nunes, Abigail Oliver, Joel Naftalin, Stewart Pringle, Kalpana Rao, Penny Robshaw, Jackie Ross, Anupama Shahid, Martyn Underwood, Nirmala Vaithilingham, and Linda Watkins; Janet Scollen for her outstanding contribution to recruitment and randomisation and all the other MifeMiso research nurses and midwives who assisted in collection of data; Mary Nulty and Hannah Noordali for support in administering the trial; Lee Middleton for his statistical support in the design of the trial; Rajendra Rai for chairing the trial steering committee; Maya Al-Memar and Ruth Bender-Atik for participating in the trial steering committee; Abha Maheshwari for chairing the data monitoring committee; Neelam Potdar and Mike Bradburn for participating in the data monitoring committee; and all those not otherwise mentioned above who have contributed to the MifeMiso trial.
Publisher Copyright:
© 2020
Keywords
- Abortion, Missed/drug therapy
- Adult
- Double-Blind Method
- Drug Therapy, Combination
- Humans
- Mifepristone/therapeutic use
- Misoprostol/therapeutic use
- Oxytocics/therapeutic use
- Treatment Outcome
ASJC Scopus subject areas
- Medicine(all)