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

被引：94

作者：

Chu, Justin J. ^{[1
]}

Devall, Adam J. ^{[1
]}

Beeson, Leanne E. ^{[2
]}

Hardy, Pollyanna ^{[2
]}

Cheed, Versha ^{[2
]}

Sun, Yongzhong ^{[2
]}

Roberts, Tracy E. ^{[2
]}

Ogwulu, C. Okeke ^{[2
]}

Williams, Eleanor ^{[2
]}

Jones, Laura L. ^{[2
]}

Papadopoulos, Jenny H. La Fontaine ^{[2
]}

Bender-Atik, Ruth ^{[3
]}

Brewin, Jane ^{[4
]}

Hinshaw, Kim ^{[5
]}

Choudhary, Meenakshi ^{[6
]}

Ahmed, Amna ^{[5
]}

Naftalin, Joel ^{[7
]}

Nunes, Natalie ^{[8
]}

Oliver, Abigail ^{[9
]}

Izzat, Feras ^{[10
]}

Bhatia, Kalsang ^{[11
]}

Hassan, Ismail ^{[12
]}

Jeve, Yadava ^{[12
]}

Hamilton, Judith ^{[13
]}

Deb, Shilpa ^{[14
]}

Bottomley, Cecilia ^{[7
]}

Ross, Jackie ^{[15
]}

Watkins, Linda ^{[16
]}

Underwood, Martyn ^{[17
]}

Cheong, Ying ^{[18
]}

Kumar, Chitra S. ^{[19
]}

Gupta, Pratima ^{[20
]}

Small, Rachel ^{[20
]}

Pringle, Stewart ^{[19
]}

Hodge, Frances ^{[21
]}

Shahid, Anupama ^{[22
]}

Gallos, Ioannis D. ^{[1
]}

Horne, Andrew W. ^{[23
]}

Quenby, Siobhan ^{[24
]}

Coomarasamy, Arri ^{[1
]}

机构：

[1] Univ Birmingham, Coll Med & Dent Sci, Inst Metab & Syst Res, Birmingham B15 2TT, W Midlands, England

[2] Univ Birmingham, Coll Med & Dent Sci, Inst Appl Hlth Res, Birmingham, W Midlands, England

[3] Miscarriage Assoc, Wakefield, England

[4] Tommys Char, London, England

[5] SouthTyneside & Sunderland NHS Fdn Trust, Sunderland Royal Hosp, Sunderland, Tyne & Wear, England

[6] Newcastle Upon Tyne Hosp NHS Fdn Trust, Royal Victoria Infirm, Newcastle Upon Tyne, Tyne & Wear, England

[7] Univ Coll London Hosp NHS Fdn Trust, Univ Coll Hosp, London, England

[8] Chelsea & Westminster NHS Fdn Trust, West Middlesex Univ Hosp, London, England

[9] Univ Hosp Bristol NHS Fdn Trust, St Michaels Hosp, Bristol, Avon, England

[10] Univ Hosp Coventry & Warwickshire NHS Trust, Univ Hosp Coventry, Coventry, W Midlands, England

[11] East Lancashire Hosp NHS Trust, Burnley Gen Hosp, Burnley, Lancs, England

[12] Birmingham Womens & Childrens NHS Fdn Trust, Birmingham Womens Hosp, Birmingham, W Midlands, England

[13] Guys & St Thomas NHS Fdn Trust, Guys & St Thomas Hosp, London, England

[14] Nottingham Univ Hosp NHS Trust, Queens Med Ctr, Nottingham, England

[15] Kings Coll Hosp NHS Fdn Trust, Kings Coll Hosp, London, England

[16] Liverpool Womens NHS Fdn Trust, Liverpool Womens Hosp, Liverpool, Merseyside, England

[17] Shrewsbury & Telford NHS Trust, Princess Royal Hosp, Telford, Shrops, England

[18] Univ Southampton, Dept Reprod Med, Southampton, Hants, England

[19] NHS Greater Glasgow & Clyde, Glasgow, Lanark, Scotland

[20] Univ Hosp Birmingham NHS Fdn Trust, Birmingham Heartlands Hosp, Birmingham, W Midlands, England

[21] Swansea Bay Univ Hlth Board, Singleton Hosp, Swansea, W Glam, Wales

[22] Royal London Hosp, Barts Hlth NHS Trust, London, England

[23] NHS Lothian, Royal Infirm Edinburgh, Edinburgh, Midlothian, Scotland

[24] Univ Warwick, Biomed Res Unit Reprod Hlth, Warwick, England

来源：

LANCET | 2020年 / 396卷 / 10253期

基金：

英国医学研究理事会;

关键词：

EARLY-PREGNANCY FAILURE; MEDICAL-MANAGEMENT; WOMEN;

D O I：

10.1016/S0140-6736(20)31788-8

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 mu g 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. Copyright Crown Copyright (C) 2020 Published by Elsevier Ltd.

引用

页码：770 / 778

页数：9

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