The University of Southampton
University of Southampton Institutional Repository
Warning ePrints Soton is experiencing an issue with some file downloads not being available. We are working hard to fix this. Please bear with us.

Mifepristone and misoprostol versus misoprostol alone for the management of missed miscarriage (MifeMiso): a randomised, double-blind, placebo-controlled trial

Mifepristone and misoprostol versus misoprostol alone for the management of missed miscarriage (MifeMiso): a randomised, double-blind, placebo-controlled trial
Mifepristone and misoprostol versus misoprostol alone for the management of missed miscarriage (MifeMiso): a randomised, double-blind, placebo-controlled trial

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.

0140-6736
770-778
Chu, Justin
71d12efa-6e26-4855-838d-7ec61df200c3
Devall, Adam
7dbbbc78-994d-4719-9269-8b75f45fb417
Beeson, Leanne
231c7abe-e7d5-4551-ae8e-5791b930ab25
Hardy, Pollyanna
6a9c6df8-9e5b-4300-8fc7-03fed7b390bd
Cheed, Versha
2024c48b-9321-4763-9df4-6dd0a1df658f
Sun, Yongzhong
81a37567-2cc1-40f0-b136-8d3f34c9340d
Roberts, Tracy
ace98789-7fc3-45f9-b2ed-1969222f32fd
Ogwulu, C. Okeke
353469bf-66be-40bd-a821-f770703704ea
Williams, Eleanor
2482d7d3-f579-4ba6-955f-21dee3050d2f
Jones, Laura
c57524cc-5920-449e-8d42-bcad0c124075
La Fontaine Papadopoulos, Jenny
f8f7c6a7-1974-4838-a06c-b2dc6f4cc6ba
Bender-Atik, Ruth
9cf86f26-fe7f-4bd3-91e4-c062e755f86e
Brewin, Jane
3882fd86-232e-4fb8-a33b-0d62ba899e3a
Hinshaw, Kim
b5eb9291-fb21-4f09-b61a-4206971143a7
Choudhary, Meenakshi
85b0e9fb-1dcb-4195-8340-2762c120fd72
Ahmed, Amna
b3c3eee2-6fae-4fda-8c7e-bed1540fba8b
Naftalin, Joel
d3f47adc-3de2-4e94-9148-f907c3027a9d
Nunes, Natalie
1a9f1ec7-f86f-4d8b-b95e-a378e2f7c21c
Oliver, Abigail
e303d303-bb3e-4bcb-91ca-cf157764a663
Izzat, Feras
880d5cf5-41b0-470b-825c-4bfb518afb21
Bhatia, Kalsang
d62eb1d3-9f02-49f6-894a-2c7a9f0a9c6e
Hassan, Ismail
9cb10d60-53f5-45df-b66b-2afa5d7e9ff3
Jeve, Yadava
839a9b03-f17c-476b-9e7f-e4e94d34ebac
Hamilton, Judith
62a165cb-3fa3-4808-8462-dd8bacaf9afc
Deb, Shilpa
60d071c4-c759-40b4-bac8-b00368e1ad60
Bottomley, Cecilia
de3e9f43-529d-4e5e-82a4-186a000e9589
Ross, Jackie
c623ffb9-f8b5-4ee6-b243-f03f66235cbb
Watkins, Linda
2631e484-8415-4695-9f69-d8fd7e7a4564
Underwood, Martyn
bd7beea0-fd12-47ba-967e-5d90c989fa6c
Cheong, Ying
4efbba2a-3036-4dce-82f1-8b4017952c83
Kumar, Chitra
4f1c74ec-6b47-49e2-9a8c-a3e459b6d614
Gupta, Pratima
06816a3e-eb27-4078-b9f9-0f1a57a28444
Small, Rachel
23900d37-3684-43b4-98f4-5974621b4c6c
Pringle, Stewart
f45925b0-d412-44ed-b326-d35badef895f
Hodge, Frances
ab1e2d44-0217-4473-b2b1-4dcfdff29d5d
Shahid, Anupama
7af4027e-933a-4e13-8223-4b780136b5ea
Gallos, Ioannis
515f746a-c10e-4a21-b33c-dfef1212f4ab
Horne, Andrew
23ea3e5c-fd9b-4d19-a170-2b9fe1b90080
Quenby, Siobhan
3fd970ad-bd8c-4e1c-8aae-0b1364dffcba
Coomarasamy, Arri
19f618a5-ab94-4378-88ad-1a61ae83ec25
Chu, Justin
71d12efa-6e26-4855-838d-7ec61df200c3
Devall, Adam
7dbbbc78-994d-4719-9269-8b75f45fb417
Beeson, Leanne
231c7abe-e7d5-4551-ae8e-5791b930ab25
Hardy, Pollyanna
6a9c6df8-9e5b-4300-8fc7-03fed7b390bd
Cheed, Versha
2024c48b-9321-4763-9df4-6dd0a1df658f
Sun, Yongzhong
81a37567-2cc1-40f0-b136-8d3f34c9340d
Roberts, Tracy
ace98789-7fc3-45f9-b2ed-1969222f32fd
Ogwulu, C. Okeke
353469bf-66be-40bd-a821-f770703704ea
Williams, Eleanor
2482d7d3-f579-4ba6-955f-21dee3050d2f
Jones, Laura
c57524cc-5920-449e-8d42-bcad0c124075
La Fontaine Papadopoulos, Jenny
f8f7c6a7-1974-4838-a06c-b2dc6f4cc6ba
Bender-Atik, Ruth
9cf86f26-fe7f-4bd3-91e4-c062e755f86e
Brewin, Jane
3882fd86-232e-4fb8-a33b-0d62ba899e3a
Hinshaw, Kim
b5eb9291-fb21-4f09-b61a-4206971143a7
Choudhary, Meenakshi
85b0e9fb-1dcb-4195-8340-2762c120fd72
Ahmed, Amna
b3c3eee2-6fae-4fda-8c7e-bed1540fba8b
Naftalin, Joel
d3f47adc-3de2-4e94-9148-f907c3027a9d
Nunes, Natalie
1a9f1ec7-f86f-4d8b-b95e-a378e2f7c21c
Oliver, Abigail
e303d303-bb3e-4bcb-91ca-cf157764a663
Izzat, Feras
880d5cf5-41b0-470b-825c-4bfb518afb21
Bhatia, Kalsang
d62eb1d3-9f02-49f6-894a-2c7a9f0a9c6e
Hassan, Ismail
9cb10d60-53f5-45df-b66b-2afa5d7e9ff3
Jeve, Yadava
839a9b03-f17c-476b-9e7f-e4e94d34ebac
Hamilton, Judith
62a165cb-3fa3-4808-8462-dd8bacaf9afc
Deb, Shilpa
60d071c4-c759-40b4-bac8-b00368e1ad60
Bottomley, Cecilia
de3e9f43-529d-4e5e-82a4-186a000e9589
Ross, Jackie
c623ffb9-f8b5-4ee6-b243-f03f66235cbb
Watkins, Linda
2631e484-8415-4695-9f69-d8fd7e7a4564
Underwood, Martyn
bd7beea0-fd12-47ba-967e-5d90c989fa6c
Cheong, Ying
4efbba2a-3036-4dce-82f1-8b4017952c83
Kumar, Chitra
4f1c74ec-6b47-49e2-9a8c-a3e459b6d614
Gupta, Pratima
06816a3e-eb27-4078-b9f9-0f1a57a28444
Small, Rachel
23900d37-3684-43b4-98f4-5974621b4c6c
Pringle, Stewart
f45925b0-d412-44ed-b326-d35badef895f
Hodge, Frances
ab1e2d44-0217-4473-b2b1-4dcfdff29d5d
Shahid, Anupama
7af4027e-933a-4e13-8223-4b780136b5ea
Gallos, Ioannis
515f746a-c10e-4a21-b33c-dfef1212f4ab
Horne, Andrew
23ea3e5c-fd9b-4d19-a170-2b9fe1b90080
Quenby, Siobhan
3fd970ad-bd8c-4e1c-8aae-0b1364dffcba
Coomarasamy, Arri
19f618a5-ab94-4378-88ad-1a61ae83ec25

Chu, Justin, Devall, Adam, Beeson, Leanne, Hardy, Pollyanna, Cheed, Versha, Sun, Yongzhong, Roberts, Tracy, Ogwulu, C. Okeke, Williams, Eleanor, Jones, Laura, La Fontaine Papadopoulos, Jenny, Bender-Atik, Ruth, Brewin, Jane, Hinshaw, Kim, Choudhary, Meenakshi, Ahmed, Amna, Naftalin, Joel, Nunes, Natalie, Oliver, Abigail, Izzat, Feras, Bhatia, Kalsang, Hassan, Ismail, Jeve, Yadava, Hamilton, Judith, Deb, Shilpa, Bottomley, Cecilia, Ross, Jackie, Watkins, Linda, Underwood, Martyn, Cheong, Ying, Kumar, Chitra, Gupta, Pratima, Small, Rachel, Pringle, Stewart, Hodge, Frances, Shahid, Anupama, Gallos, Ioannis, Horne, Andrew, Quenby, Siobhan and Coomarasamy, Arri (2020) Mifepristone and misoprostol versus misoprostol alone for the management of missed miscarriage (MifeMiso): a randomised, double-blind, placebo-controlled trial. The Lancet, 396 (10253), 770-778. (doi:10.1016/S0140-6736(20)31788-8).

Record type: Article

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.

This record has no associated files available for download.

More information

Accepted/In Press date: 1 January 2020
e-pub ahead of print date: 24 August 2020
Published date: 12 September 2020

Identifiers

Local EPrints ID: 443766
URI: http://eprints.soton.ac.uk/id/eprint/443766
ISSN: 0140-6736
PURE UUID: d05dc005-5389-4f4f-ab02-19991241f2f5
ORCID for Ying Cheong: ORCID iD orcid.org/0000-0001-7687-4597

Catalogue record

Date deposited: 11 Sep 2020 16:30
Last modified: 26 Nov 2021 02:53

Export record

Altmetrics

Contributors

Author: Justin Chu
Author: Adam Devall
Author: Leanne Beeson
Author: Pollyanna Hardy
Author: Versha Cheed
Author: Yongzhong Sun
Author: Tracy Roberts
Author: C. Okeke Ogwulu
Author: Eleanor Williams
Author: Laura Jones
Author: Jenny La Fontaine Papadopoulos
Author: Ruth Bender-Atik
Author: Jane Brewin
Author: Kim Hinshaw
Author: Meenakshi Choudhary
Author: Amna Ahmed
Author: Joel Naftalin
Author: Natalie Nunes
Author: Abigail Oliver
Author: Feras Izzat
Author: Kalsang Bhatia
Author: Ismail Hassan
Author: Yadava Jeve
Author: Judith Hamilton
Author: Shilpa Deb
Author: Cecilia Bottomley
Author: Jackie Ross
Author: Linda Watkins
Author: Martyn Underwood
Author: Ying Cheong ORCID iD
Author: Chitra Kumar
Author: Pratima Gupta
Author: Rachel Small
Author: Stewart Pringle
Author: Frances Hodge
Author: Anupama Shahid
Author: Ioannis Gallos
Author: Andrew Horne
Author: Siobhan Quenby
Author: Arri Coomarasamy

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×