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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
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Hardy, Pollyanna
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Williams, Eleanor
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Hinshaw, Kim
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Bhatia, Kalsang
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Hassan, Ismail
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Hamilton, Judith
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Deb, Shilpa
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Bottomley, Cecilia
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Ross, Jackie
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Cheong, Ying
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Chu, Justin
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Devall, Adam
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Cheed, Versha
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Roberts, Tracy
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Williams, Eleanor
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Jones, Laura
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La Fontaine Papadopoulos, Jenny
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Bender-Atik, Ruth
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Brewin, Jane
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Bhatia, Kalsang
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Hassan, Ismail
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Bottomley, Cecilia
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Ross, Jackie
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Cheong, Ying
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Small, Rachel
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Horne, Andrew
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Coomarasamy, Arri
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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.

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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

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Date deposited: 11 Sep 2020 16:30
Last modified: 16 Aug 2024 01:42

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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

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