CLINICAL ARTICLE Titrated oral misoprostol solution versus vaginal misoprostol for labor induction Alex S.R. Souza a,b,c,d,e, ⁎, Francisco E.L. Feitosa f , Aurélio A.R. Costa a,e , Ana P.R. Pereira a , Andreza S. Carvalho a , Renata M. Paixão a , Leila Katz a,d , Melania M.R. Amorim a,d,g a Department of Maternal and Child Health, Instituto de Medicina Integral Prof. Fernando Figueira, Recife, Brazil b Emergency Obstetric Care, Policlínica e Maternidade Prof. Arnaldo Marques, Recife, Brazil c Department of Maternal and Child Health, Universidade Federal de Pernambuco, Recife, Brazil d Research Department, Instituto de Pesquisa Prof. Joaquim Amorim Neto, Campina Grande, Brazil e Emergency Obstetric Care, Hospital Barão de Lucena, Recife, Brazil f Department of Obstetrics, Universidade Federal do Ceará, Fortaleza, Brazil g Department of Obstetrics, Universidade Federal de Campina Grande, Campina Grande, Brazil abstract article info Article history: Received 20 March 2013 Received in revised form 13 June 2013 Accepted 28 August 2013 Keywords: Clinical trial Induced labor Misoprostol Objective: To determine the efficacy and safety of a titrated oral misoprostol solution compared with vaginal mi- soprostol tablets for labor induction. Methods: A randomized, triple-blind, multicenter clinical trial was con- ducted between March 2010 and June 2011. Women with a single gestation (n = 200) were randomized to receive a titrated oral misoprostol solution (initial misoprostol dose 20 μg/hour; dose increased by 20 μg/hour every 6 hours up to 80 μg/hour for a maximum of 48 doses) or vaginal misoprostol tablets (25 μg of misoprostol every 6 hours for a maximum of 8 doses). Risk ratios (RR) and 95% confidence intervals (CIs) were calculated for maternal and perinatal outcomes. Results: The frequencies of vaginal delivery not achieved within 12 hours (RR 0.87; 95% CI, 0.62–1.22) and within 24 hours (RR 1.11; 95% CI, 0.83–1.49) were similar in the 2 groups. No differ- ences were found in terms of uterine hyperstimulation, unfavorable cervix at 12 and 24 hours, oxytocin augmen- tation, tachysystole, epidural analgesia, adverse effects, and perinatal outcome. Approximately 70% of the women preferred the oral solution. Conclusion: A titrated oral misoprostol solution was as effective and safe for labor in- duction as vaginal misoprostol tablets. ClinicalTrial.gov: NCT00 992524 © 2013 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. 1. Introduction Misoprostol is one of the most common methods used to induce labor and can be administered by various routes and using several treat- ment regimens. The frequency of induced births depends on the country and region, with an estimated average of 20% of births [1–8]. The effec- tiveness of misoprostol is no longer questioned, although the ideal dose and route of administration remain to be defined [3–10]. The WHO [1] recommends 25 μg of oral misoprostol every 2 hours or 25 μg of vaginal misoprostol every 6 hours (strong recommendation). In an open randomized clinical trial [8], a titrated oral misoprostol solution was shown to be of exceptional benefit, with a lower rate of uterine hyperstimulation and higher rates of nausea and vaginal de- livery in the oral solution group compared with vaginal misoprostol. However, other studies [11–15] have failed to confirm the superiority of this regimen. A lower-dose regimen with shorter dosing intervals seems to be in accordance with the pharmacokinetics of oral compared with vaginal misoprostol [8–10]. Although previous studies [8,11,12,14] have evalu- ated the use of a titrated misoprostol solution, none used a homoge- nized oral solution. The present study was conducted to determine the effectiveness and safety of a titrated oral homogenized misoprostol solution compared with vaginal misoprostol tablets for the induction of labor in full-term live pregnancies. 2. Materials and methods A multicenter randomized, triple-blind clinical trial was carried out at Instituto de Medicina Integral Professor Fernando Figueira (IMIP), Policlínica e Maternidade Professor Arnaldo Marques, and Hospital Barão de Lucena, all in the city of Recife, Pernambuco, in northeastern Brazil, between March 1, 2010, and June 30, 2011. The study was International Journal of Gynecology and Obstetrics 123 (2013) 207–212 ⁎ Corresponding author at: Avenida Rui Barbosa 579, Ap. 406, Graças, 52 011–040 Recife, Pernambuco, Brazil. Tel./fax: +55 81 2122 4122. E-mail address: alexrolland@uol.com.br (A.S.R. Souza). 0020-7292/$ – see front matter © 2013 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijgo.2013.06.028 Contents lists available at ScienceDirect International Journal of Gynecology and Obstetrics journal homepage: www.elsevier.com/locate/ijgo