Official Title: “Oral Misoprostol Titrated Solution Versus Vaginal Misoprostol for Induction of Labour: Randomized Controlled Trial”

The purpose of this study is to compare effectiveness and safety of an oral titrated solution of misoprostol with vaginal misoprostol for induction of labour with an alive fetus.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: August 2011

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.

Intervention(s) in this Clinical Trial

• Drug: Misoprostol
  • 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.
• Drug: Misoprostol
  • Vaginal tablets will have 25mcg of misoprostol or placebo.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: Oral Titrated Misoprostol Solution
• Active Comparator: Vaginal Misoprostol

Primary Measures

• Vaginal delivery
  • Time Frame: 24 hours
    Safety Issue?: No
• Hyperstimulation syndrome
  • Time Frame: 24 hours
    Safety Issue?: Yes
• Cesarean section
  • Time Frame: 3 days
    Safety Issue?: No
• Severe neonatal morbidity or perinatal death
  • Time Frame: 28 days
    Safety Issue?: Yes
• Serious maternal morbidity or maternal death
  • Time Frame: 42
    Safety Issue?: Yes

Secondary Measures

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

Inclusion Criteria:

• Indication for labour induction
• Term pregnancy with alive fetus
• Bishop score less than six

Exclusion Criteria:

• Age less than 18 years
• Previous uterine scar
• Nonvertex presentation
• Non-reassuring fetal status
• Fetal anomalies
• Fetal growth restriction
• Genital bleeding
• Tumors, malformations and/or ulcers of vulva, perineum or vagina

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 50 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Instituto Materno Infantil Prof. Fernando Figueira

Overall Clinical Trial Officials and Contacts

Alex SR Souza, Phd student Study Chair Instituto de Medicina Integral Professor Fernando Figueira (IMIP)  

Overall Contact: Alex SR Souza, PhD student 55-81-32217924 alexrolland@uol.com.br

Information obtained from ClinicalTrials.gov on February 04, 2010

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00992524

Study ID Number: ORALTIMI

ClinicalTrials.gov Identifier: NCT00992524

Health Authority: Brazil: National Health Surveillance Agency