Mifepristone and misoprostol versus placebo and misoprostol for resolution of miscarriage in women diagnosed with missed miscarriage: the MifeMiso RCT

Health Technology Assessment

Anupama Shahid¹  Siobhan Quenby²  Rachel Small³  Pratima Gupta³  Yadava Jeve⁴  Ismail Hassan⁴  Kalsang Bhatia⁵  Cecilia Bottomley⁶  Ying Cheong⁷  Chitra Kumar⁸  Judith Hamilton⁹  Leanne Beeson^1,10  Eleanor Williams^1,10  Yongzhong Sun^1,10  Jenny La Fontaine Papadopoulos^1,10  Laura Jones^1,10  Versha Cheed^1,10  Tracy Roberts^1,10  Chidubem Okeke Ogwulu^1,10  Justin Chu^1,11  Adam Devall^1,11  Ioannis Gallos^1,11  Arri Coomarasamy^1,11  Jackie Ross^1,12  Linda Watkins^1,13  Andrew Horne^1,14  Ruth Bender-Atik^1,15  Pollyanna Hardy^1,16  Martyn Underwood^1,17  Stewart Pringle^1,18  Shilpa Deb^1,19  Meenakshi Choudhary^2,20  Frances Hodge^2,21  Abigail Oliver^2,22  Amna Ahmed^2,23  Kim Hinshaw^2,23  Jane Brewin^2,24  Joel Naftalin^2,25  Feras Izzat^2,26  Natalie Nunes^2,27 

[1] Barts Health NHS Trust, Royal London Hospital, London, UK;Biomedical Research Unit in Reproductive Health, University of Warwick, Coventry, UK;Birmingham Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK;Birmingham Women’s Hospital, Birmingham Women’s and Children’s NHS Foundation Trust, Birmingham, UK;Burnley General Hospital, East Lancashire Hospitals NHS Trust, Burnley, UK;Chelsea and Westminster Hospital, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK;Department of Reproductive Medicine, University of Southampton, Southampton, UK;Glasgow Royal Infirmary, NHS Greater Glasgow and Clyde, Glasgow, UK;Guy’s and St Thomas’ Hospital, Guy’s and St Thomas’ NHS Foundation Trust, London, UK;Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK;Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK;King’s College Hospital, King’s College Hospital NHS Foundation Trust, London, UK;Liverpool Women’s Hospital, Liverpool Women’s NHS Foundation Trust, Liverpool, UK;MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK;Miscarriage Association, Wakefield, UK;National Perinatal Epidemiology Unit Clinical Trials Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK;Princess Royal Hospital, Shrewsbury and Telford Hospital NHS Trust, Telford, UK;Queen Elizabeth University Hospital, NHS Greater Glasgow and Clyde, Glasgow, UK;Queen’s Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK;Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK;Singleton Hospital, Swansea Bay University Health Board, Swansea, UK;St Michael’s Hospital, University Hospitals Bristol NHS Foundation Trust, Bristol, UK;Sunderland Royal Hospital, South Tyneside & Sunderland NHS Foundation Trust, Sunderland, UK;Tommy’s Charity, London, UK;University College Hospital, University College London Hospitals NHS Foundation Trust, London, UK;University Hospital Coventry, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK;West Middlesex University Hospital, Chelsea and Westminster Hospital NHS Foundation Trust, Isleworth, UK;

关键词: pregnancy;    mifepristone;    misoprostol;    missed miscarriage;    medical management;    gestational sac;    randomised controlled trial;   

DOI  :  10.3310/hta25680

来源: DOAJ

【 摘 要 】

Trial design: A randomised, parallel-group, double-blind, placebo-controlled multicentre study with health economic and nested qualitative studies to determine if mifepristone (Mifegyne®, Exelgyn, Paris, France) plus misoprostol is superior to misoprostol alone for the resolution of missed miscarriage. Methods: Women diagnosed with missed miscarriage in the first 14 weeks of pregnancy were randomly assigned (1 : 1 ratio) to receive 200 mg of oral mifepristone or matched placebo, followed by 800 μg of misoprostol 2 days later. A web-based randomisation system allocated the women to the two groups, with minimisation for age, body mass index, parity, gestational age, amount of bleeding and randomising centre. The primary outcome was failure to pass the gestational sac within 7 days after randomisation. The prespecified key secondary outcome was requirement for surgery to resolve the miscarriage. A within-trial cost-effectiveness study and a nested qualitative study were also conducted. Women who completed the trial protocol were purposively approached to take part in an interview to explore their satisfaction with and the acceptability of medical management of missed miscarriage. Results: A total of 711 women, from 28 hospitals in the UK, were randomised to receive either mifepristone plus misoprostol (357 women) or placebo plus misoprostol (354 women). The follow-up rate for the primary outcome was 98% (696 out of 711 women). The risk of failure to pass the gestational sac within 7 days was 17% (59 out of 348 women) in the mifepristone plus misoprostol group, compared with 24% (82 out of 348 women) in the placebo plus misoprostol group (risk ratio 0.73, 95% confidence interval 0.54 to 0.98; p = 0.04). Surgical intervention to resolve the miscarriage was needed in 17% (62 out of 355 women) in the mifepristone plus misoprostol group, compared with 25% (87 out of 353 women) in the placebo plus misoprostol group (risk ratio 0.70, 95% confidence interval 0.52 to 0.94; p = 0.02). There was no evidence of a difference in the incidence of adverse events between the two groups. A total of 42 women, 19 in the mifepristone plus misoprostol group and 23 in the placebo plus misoprostol group, took part in an interview. Women appeared to have a preference for active management of their miscarriage. Overall, when women experienced care that supported their psychological well-being throughout the care pathway, and information was delivered in a skilled and sensitive manner such that women felt informed and in control, they were more likely to express satisfaction with medical management. The use of mifepristone and misoprostol showed an absolute effect difference of 6.6% (95% confidence interval 0.7% to 12.5%). The average cost per woman was lower in the mifepristone plus misoprostol group, with a cost saving of £182 (95% confidence interval £26 to £338). Therefore, the use of mifepristone and misoprostol for the medical management of a missed miscarriage dominated the use of misoprostol alone. Limitations: The results from this trial are not generalisable to women diagnosed with incomplete miscarriage and the study does not allow for a comparison with expectant or surgical management of miscarriage. Future work: Future work should use existing data to assess and rank the relative clinical effectiveness and safety profiles for all methods of management of miscarriage. Conclusions: Our trial showed that pre-treatment with mifepristone followed by misoprostol resulted in a higher rate of resolution of missed miscarriage than misoprostol treatment alone. Women were largely satisfied with medical management of missed miscarriage and would choose it again. The mifepristone and misoprostol intervention was shown to be cost-effective in comparison to misoprostol alone. Trial registration: Current Controlled Trials ISRCTN17405024. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 68. See the NIHR Journals Library website for further project information.

【 授权许可】

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