Misoprostol dose and route after mifepristone for early medical abortion: a randomised controlled noninferiority trial

Please cite this paper as: von Hertzen H, Huong N, Piaggio G, Bayalag M, Cabezas E, Fang A, Gemzell‐Danielsson K, Hinh N, Mittal S, Ng E, Chaturachinda K, Pinter B, Puscasiu L, Savardekar L, Shenoy S, Khomassuridge A, Tuyet H, Velasco A, Peregoudov A, for the WHO Research Group on Postovulatory Methods of Fertility Regulation. Misoprostol dose and route after mifepristone for early medical abortion: a randomised controlled noninferiority trial. BJOG 2010;117:1186–1196. Objective To compare 400 and 800 μg sublingual or vaginal misoprostol 24 hours after 200 mg mifepristone for noninferiority regarding efficacy in achieving complete abortion for pregnancy termination up to 63 days of gestation. Design Placebo‐controlled, randomised, noninferiority factorial trial, stratified by centre and length of gestation. Misoprostol 400 or 800 μg, administered either sublingually or vaginally, with follow up after 2 and 6 weeks. Setting Fifteen obstetrics/gynaecology departments in ten countries. Population Pregnant women (n = 3005) up to 63 days of gestation requesting medical abortion. Methods Two‐sided 95% CI for differences in failure of complete abortion and continuing pregnancy, with a 3% noninferiority margin, were calculated. Proportions of women with adverse effects were recorded. Outcome measures Complete abortion without surgical intervention (main); continuing live pregnancies, induction‐to‐abortion interval, adverse effects, women’s perceptions (secondary). Results Efficacy outcomes analysed for 2962 women (98.6%): 90.5% had complete abortion after 400 μg misoprostol, 94.2% after 800 μg. Noninferiority of 400 μg misoprostol was not demonstrated for failure of complete abortion (difference: 3.7%; 95% CI 1.8–5.6%). The 400‐μg dose showed higher risk of incomplete abortion (P