Oral Titrated Misoprostol for Induction of Labour (OTISMISO)

• Vaginal delivery [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  
• Hyperstimulation syndrome [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
  
• Cesarean section [ Time Frame: 3 days ] [ Designated as safety issue: No ]
  
• Severe neonatal morbidity or perinatal death [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  
• Serious maternal morbidity or maternal death [ Time Frame: 42 ] [ Designated as safety issue: Yes ]
  

• Need of oxytocin for augmentation of labour [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
  
• Number of doses needed to bring on labour [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
  
• Interval from 1st dose to labour [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
  
• Interval from 1st dose to delivery [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
  
• Failed induction [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
  
• Tachysystole [ Time Frame: 48 hours ] [ Designated as safety issue: Yes ]
  
• Uterine rupture [ Time Frame: 72 houras ] [ Designated as safety issue: Yes ]
  
• Need of labour analgesia [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
  
• Instrumental delivery [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
  
• Side effects: nausea, vomit, diarrhea, postpartum haemorrhage [ Time Frame: 72 hours ] [ Designated as safety issue: Yes ]
  
• Maternal death [ Time Frame: 42 days ] [ Designated as safety issue: Yes ]
  
• Meconium [ Time Frame: 72 hours ] [ Designated as safety issue: Yes ]
  
• Non-reassuring fetal heart rate [ Time Frame: 72 hours ] [ Designated as safety issue: Yes ]
  
• Apgar scores less than 7 at 1st and 5th minute [ Time Frame: 1st and 5th minutes after delivery ] [ Designated as safety issue: Yes ]
  
• Admission at neonatal intensive care unit [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  
• Perinatal or neonatal death [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  
• Neonatal encephalopathy [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  
• Women not satisfied with route of drug administration [ Time Frame: 48 hours after delivery ] [ Designated as safety issue: Yes ]
  

Several methods for induction of labour are available. However, the most effective and with less frequency of adverse effects is still unknown. Vaginal misoprostol has been used frequently to induce labour but other routes of administrations have been proposed, such as oral, sublingual and, more recently, oral titrated solution. The purpose of this study is to compare effectiveness and safety of this oral misoprostol titrated solution with vaginal misoprostol administration for induction of labour with an alive fetus. A randomized controlled double-blind trial will be carried in three hospitals: Instituto de Medicina Integral Prof. Fernando Figueira, Universidade Federal do Ceará and Instituto de Saúde Elpídio de Almeida, from November 2009 to November 2011. A total of 400 patients must be enrolled. Inclusion criteria are: a) indication for labour induction; b) term pregnancy with alive fetus; Bishop score less than six. Exclusion criteria are: a) age less than 18 years; b) previous uterine scar; c) nonvertex presentation; d) non-reassuring fetal status; e) fetal anomalies; f) fetal growth restriction; g) genital bleeding; h) tumors, malformations and/or ulcers of vulva, perineum or vagina. They will be randomized to receive an oral misoprostol titrated solution with vaginal placebo tablet or oral placebo solution with vaginal misoprostol tablet. Oral solution will have misoprostol at a concentration of 2mcg/ml or placebo. Vaginal tablets will have 25mcg of misoprostol or placebo. Oral solution dose will be 20mcg/hour (misoprostol) or 10ml/hour (placebo) in the first six hours with an increase of 20mcg/hour (10ml/hour) of misoprostol or placebo each six hours if labour does not start, until the maximum dose of 80mcg/hour or 40ml/hour in the first 24 hours. This maximum dose can be maintained for more 24 hours if needed. Vaginal misoprostol or placebo tablets will be administered for each six hours until the maximum dose of 200mcg or eight tablets. Primary outcomes will be vaginal delivery within 24 hours, hyperstimulation syndrome, cesarean section, severe neonatal morbidity or perinatal death, serious maternal morbidity or maternal death. Secondary outcomes will be need of oxytocin for augmentation of labour, number of misoprostol doses needed to bring on labour, interval from first dose to labour and first dose to delivery, failed induction, tachysystole, uterine rupture, need of labour analgesia, instrumental delivery, side effects, maternal death, meconium, non-reassuring fetal heart rate, Apgar scores less than seven at 1st and 5th minutes, admission at neonatal intensive care unit, neonatal encephalopaty, perinatal death and women not satisfied.