Mifepristone and misoprostol versus misoprostol alone for the management of missed miscarriage (MifeMiso): a randomised, double-blind, placebo-controlled trial.
Journal
Lancet (London, England)
ISSN: 1474-547X
Titre abrégé: Lancet
Pays: England
ID NLM: 2985213R
Informations de publication
Date de publication:
12 09 2020
12 09 2020
Historique:
received:
11
07
2020
revised:
24
07
2020
accepted:
06
08
2020
pubmed:
28
8
2020
medline:
7
10
2020
entrez:
28
8
2020
Statut:
ppublish
Résumé
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. 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 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. 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. UK National Institute for Health Research Health Technology Assessment Programme.
Sections du résumé
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
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.
Identifiants
pubmed: 32853559
pii: S0140-6736(20)31788-8
doi: 10.1016/S0140-6736(20)31788-8
pmc: PMC7493715
pii:
doi:
Substances chimiques
Oxytocics
0
Misoprostol
0E43V0BB57
Mifepristone
320T6RNW1F
Types de publication
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
770-778Subventions
Organisme : Medical Research Council
ID : G0802808
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_16003
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
This is an Open Access article under the CC BY-NC-ND 4.0 license.
Références
BMJ. 2020 Jan 20;368:l6438
pubmed: 31959625
N Engl J Med. 2005 Aug 25;353(8):761-9
pubmed: 16120856
Am J Obstet Gynecol. 2020 Apr;222(4):367.e1-367.e22
pubmed: 31953115
BMJ. 1997 Jul 5;315(7099):32-4
pubmed: 9233324
Ultrasound Obstet Gynecol. 2011 May;37(5):588-95
pubmed: 21520315
N Engl J Med. 2007 Nov 22;357(21):2189-94
pubmed: 18032770
J Obstet Gynaecol India. 2018 Feb;68(1):39-44
pubmed: 29391674
Cochrane Database Syst Rev. 2012 Mar 14;(3):CD008679
pubmed: 22419336
BJOG. 2011 Mar;118 Suppl 1:1-203
pubmed: 21356004
Int J Gynaecol Obstet. 2007 Oct;99(1):46-51
pubmed: 17599843
Br J Cancer. 1976 Dec;34(6):585-612
pubmed: 795448
Fertil Steril. 2006 Oct;86(4):956-60
pubmed: 17027362
Arch Gen Psychiatry. 2000 Aug;57(8):777-84
pubmed: 10920466
Cochrane Database Syst Rev. 2019 Jun 17;6:CD002253
pubmed: 31206170
Clin Obstet Gynecol. 2007 Mar;50(1):67-88
pubmed: 17304025
BMJ. 2013 Jun 19;346:f3676
pubmed: 23783355
Cochrane Database Syst Rev. 2006 Jul 19;(3):CD002253
pubmed: 16855990
Eur J Obstet Gynecol Reprod Biol. 2014 Dec;183:16-9
pubmed: 25461345
Obstet Gynecol. 2018 Nov;132(5):e197-e207
pubmed: 30157093
Obstet Gynecol. 2006 Apr;107(4):901-7
pubmed: 16582130
Acta Obstet Gynecol Scand. 2002 Nov;81(11):1060-5
pubmed: 12421175
Pain Med. 2005 Mar-Apr;6(2):143-8
pubmed: 15773879
N Engl J Med. 2018 Jun 7;378(23):2161-2170
pubmed: 29874535