Oral Titrated Misoprostol for Induction of Labour

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Labor, Induced

Intervention / Treatment
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* Drug: Misoprostol
* Drug: Misoprostol


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Oral Titrated Misoprostol Solution<br> | Drug: Misoprostol<br>* 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.<br>* Other names: Cytotec;|
| Active Comparator: Vaginal Misoprostol<br> | Drug: Misoprostol<br>* Vaginal tablets will have 25mcg of misoprostol or placebo.<br>* Other names: Cytotec;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vaginal delivery |  | 24 hours | 
| Hyperstimulation syndrome |  | 24 hours | 
| Cesarean section |  | 3 days | 
| Severe neonatal morbidity or perinatal death |  | 28 days | 
| Serious maternal morbidity or maternal death |  | 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Need of oxytocin for augmentation of labour |  | 48 hours | 
| Number of doses needed to bring on labour |  | 48 hours | 
| Interval from 1st dose to labour |  | 48 hours | 
| Interval from 1st dose to delivery |  | 48 hours | 
| Failed induction |  | 72 hours | 
| Tachysystole |  | 48 hours | 
| Uterine rupture |  | 72 houras | 
| Need of labour analgesia |  | 48 hours | 
| Instrumental delivery |  | 48 hours | 
| Side effects: nausea, vomit, diarrhea, postpartum haemorrhage |  | 72 hours | 
| Maternal death |  | 42 days | 
| Meconium |  | 72 hours | 
| Non-reassuring fetal heart rate |  | 72 hours | 
| Apgar scores less than 7 at 1st and 5th minute |  | 1st and 5th minutes after delivery | 
| Admission at neonatal intensive care unit |  | 28 days | 
| Perinatal or neonatal death |  | 28 days | 
| Neonatal encephalopathy |  | 28 days | 
| Women not satisfied with route of drug administration |  | 48 hours after delivery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Misoprostol, Labor, Obstetric, Labor, Induced