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Objective To compare 400 and 800 lg 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 lg, 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-toabortion interval, adverse effects, women's perceptions (secondary).Results Efficacy outcomes analysed for 2962 women (98.6%): 90.5% had complete abortion after 400 lg misoprostol, 94.2% after 800 lg. Noninferiority of 400 lg misoprostol was not demonstrated for failure of complete abortion (difference: 3.7%; 95% CI 1.8-5.6%). The 400-lg dose showed higher risk of incomplete abortion (P < 0.01) and continuing pregnancy (P < 0.01) than 800 lg. Vaginal and sublingual routes had similar risks of failure to achieve complete abortion (P = 0.47, difference in sublingual minus vaginal )0.7%, 95% CI )2.6-1.2%). A similar pattern was observed for continuing pregnancies (P = 0.21). Fewer women reported adverse effects with vaginal than sublingual administration and with the 400-lg dose than the 800-lg dose. Of the women, 94% were satisfied or highly satisfied with the regimens, 53% preferred the sublingual route and 47% preferred the vaginal route.Conclusions A 400-lg dose of misoprostol should not replace the 800-lg dose when administered 24 hours after 200 mg mifepristone for inducing abortion in pregnancies up to 63 days. Sublingual and vaginal misoprostol have similar efficacy, but vaginal administration is associated with a lower frequency of adverse effects.

BackgroundObstetric hemorrhage is the leading cause of maternal mortality. Using a cluster randomized design, we investigated whether application of the Non-pneumatic Anti-Shock Garment (NASG) before transport to referral hospitals (RHs) from primary health care centers (PHCs) decreased adverse outcomes among women with hypovolemic shock. We hypothesized the NASG group would have a 50% reduction in adverse outcomes.Methods and FindingsWe randomly assigned 38 PHCs in Zambia and Zimbabwe to standard obstetric hemorrhage/shock protocols or the same protocols plus NASG prior to transport. All women received the NASG at the RH. The primary outcomes were maternal mortality; severe, end-organ failure maternal morbidity; and a composite mortality/morbidity outcome, which we labeled extreme adverse outcome (EAO). We also examined whether the NASG contributed to negative side effects and secondary outcomes. The sample size for statistical power was not reached; of a planned 2400 women, 880 were enrolled, 405 in the intervention group. The intervention was associated with a non-significant 46% reduced odds of mortality (OR 0.54, 95% CI 0.14–2.05, p = 0.37) and 54% reduction in composite EAO (OR 0.46, 95% CI 0.13–1.62, p = 0.22). Women with NASGs recovered from shock significantly faster (HR 1.25, 95% CI 1.02–1.52, p = 0.03). No differences were observed in secondary outcomes or negative effects. The main limitation was small sample size.ConclusionsDespite a lack of statistical significance, the 54% reduced odds of EAO and the significantly faster shock recovery suggest there might be treatment benefits from earlier application of the NASG for women experiencing delays obtaining definitive treatment for hypovolemic shock. As there are no other tools for shock management outside of referral facilities, and no safety issues found, consideration of NASGs as a temporizing measure during delays may be warranted. A pragmatic study with rigorous evaluation is suggested for further research.Trial RegistrationClinicalTrials.gov NCT00488462

Equivalence between vaginal and sublingual administration could not be demonstrated overall. Vaginal administration showed a higher effectiveness than sublingual administration in terminating second trimester pregnancies, but this result was mainly driven by nulliparous women. Fever was more prevalent with vaginal administration. Registered with International Standard Randomized Controlled Trial number ISRCTN72965671.

Objective To compare the efficacy of 100 mg and 200 mg of mifepristone and 24-and 48-hour intervals to administration of 800mg vaginal misoprostol for termination of early pregnancy.Design Placebo-controlled, randomized, equivalence trial, stratified by centre.Setting 13 departments of obstetrics and gynecology in nine countries.Population 2181 women with 63 days or less gestation requesting medical abortion.Methods Two-sided 95% CI for the risk differences of failure to complete abortion were calculated and compared with 5% equivalence margin between two doses of mifepristone and two intervals to misoprostol administration. Proportions of women with adverse effects were compared between the regimens using standard testes for proportions.Outcome measures Rates of complete abortion without surgical intervention and adverse effects associated with the regimens.Results Efficacy outcome was analysed for 2126 women (97.5%) excluding 55 lost to follow up. Both mifepristone doses were found to be similar in efficacy. The rate of complete abortion was 92.0% for women assigned 100 mg of mifepristone and 93.2% for women assigned 200 mg of mifepristone (difference 1.2%, 95% CI: -1.0 to 3.5). Equivalence was also evident for the two intervals of administration: the rate of complete abortion was 93.5% for 24-hour interval and 91.7% for the 48-hour interval (difference -1.8%, 95% CI: -4.0 to 0.5). Interaction between doses and interval to misoprostol administration was not significant (P = 0.92). Adverse effects related to treatments did not differ between the groups.Conclusions Both the 100 and 200 mg doses of mifepristone and the 24-and 48-hour intervals have a similar efficacy to achieve complete abortion in early pregnancy when mifepristone is followed by 800 micrograms of vaginally administered misoprostol.