Sublingual Misoprostol for Induction of Labor

Study Overview
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Brief Summary
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The purpose of this study is to compare effectiveness and safety of a sublingual misoprostol 12,5 mcg with vaginal misoprostol 25 mcg for induction of labour with an alive and term 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 and sublingual. The purpose of this study is to compare effectiveness and safety of sublingual misoprostol 12,5 mcg with vaginal misoprostol 25 mcg administration for induction of labour with an alive and term fetus. A randomized controlled double-blind trial will be carried in two hospitals: Instituto de Medicina Integral Prof. Fernando Figueira and Universidade Federal do Ceará and Instituto de Saúde Elpídio de Almeida, from July 2014 to November 2016. A total of 150 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) previous uterine scar; b) nonvertex presentation; c) non-reassuring fetal status; d) fetal anomalies; e) fetal growth restriction; f) genital bleeding; g) tumors, malformations and/or ulcers of vulva, perineum or vagina. They will be randomized to receive a sublingual misoprostol 12,5 mcg with vaginal placebo tablet or sublingual placebo with vaginal misoprostol 25 mcg tablet. Vaginal tablets will have 25mcg of misoprostol or placebo. Sublingual tablet will have 12,5mcg or placebo. Vaginal misoprostol or placebo tablets will be administered for each six hours until the maximum dose of 200mcg or eight tablets. Primary outcome will be the frequency of tachysystole. Secondary outcomes will be vaginal delivery within 24 hours, hyperstimulation syndrome, cesarean section, severe neonatal morbidity or perinatal death, serious maternal morbidity or maternal death, 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, 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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Sublingual Misoprostol 12,5 mcg Versus Vaginal Misoprostol 25 mcg for Induction of Labour of Alive and Term Fetus : Randomized Controlled Trial

Conditions
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Labor, Induced

Intervention / Treatment
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* Drug: Misoprostol 25mcg
* Drug: Sublingual 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: 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: 15 Years
Maximum Age: 45 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: Sublingual Misoprostol 12,5mcg<br>Sublingual misoprostol or placebo tablete will be administered for each six hours until the maximum dose of 100mcg or eight tablets. | Drug: Sublingual Misoprostol<br>* Sublingual misoprostol or placebo tablets will be administered for each six hours until the maximum dose of 100mcg or eight tablets<br>* Other names: Cytotec;|
| Active Comparator: Vaginal Misoprostol 25 mcg<br>Vaginal misoprostol or placebo tablets will be administered for each six hours until the maximum dose of 200mcg or eight tablets. Each pacient will receve at the same time a sublingual placebo tablet and vaginal misoprostol or sublingual misoprostol and vaginal placebo tablet. It will depend of the randomization. | Drug: Misoprostol 25mcg<br>* Vaginal misoprostol or placebo tablets will be administered for each six hours until the maximum dose of 200mcg or eight tablets.<br>* Other names: Prostokos Cytotec;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of taquissistoly | during 48 hours the presence of taquissistoly will be observed | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hyperstimulation Syndrome | during 48 hours the presence of hyperstimulation syndrome will be observed | 48 hours | 
| changes in the cervix at 12 and 24 hours | changes in the cervix | 12 and 24 hours | 
| failure to achieve vaginal delivery within 12 and 24 hours | failure to achieve vaginal delivery | 12 and 24 hours | 
| the mother's preferred route of administration | Ask to mother what route of administratios was the best for her | after 48 hours | 
| time between the first dose and the onset of labour and delivery | to avaluete the time between the first dose and the onset of labour and delivery | after 48 hours | 
| duration of labour | to avaluete the time of duration of labour | after 48 hours | 
| need for oxytocin | to avaluete the use of oxytocin during the labour | after 48 hours | 
| failed induction of labour | to avaluete the faliled induction of labor | after 48 hours | 
| Caesarean section and the indications for this procedure | to avaluete the number of Caesarean section and the indications for this procedure | after 48 hours | 
| need for epidural anaesthesia | to avaluete the need for epidural anaesthesia | after 48 hours | 
| maternal side effects (nausea, vomiting, diarrhoea, postpartum haemorrhage and fever); | to avaluete if occurred any case of maternal side effects (nausea, vomiting, diarrhoea, postpartum haemorrhage and fever); | after 48 hours | 
| severe maternal morbidity (uterine rupture, sepsis and admission to intensive care unit) or maternal death | to avaluete severe maternal morbidity (uterine rupture, sepsis and admission to intensive care unit) or maternal death | 48 hours | 
| meconium in the amniotic fluid | to avaluete meconium in the amniotic fluid | 48 hours | 
| non-reassuring foetal heart rate | non-reassuring foetal heart rate | 48 hours | 
| one- and five-minute Apgar scores <7 | to avaluete one- and five-minute Apgar scores <7 | after 48 hours | 
| admission of the newborn to a neonatal intensive care unit | to avaluete admission of the newborn to a neonatal intensive care unit | after 48 hours | 
| need for neonatal resuscitation | to avaluete the need for neonatal resuscitation | after 48 hours | 
| severe neonatal morbidity (convulsions and neonatal asphyxiation) or perinatal death. | to avaluete severe neonatal morbidity (convulsions and neonatal asphyxiation) or perinatal death. | after 48 hours | 

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