Clinical trial NCT00992524: Oral Titrated Misoprostol for Induction of Labour
Official title: Oral Misoprostol Titrated Solution Versus Vaginal Misoprostol for Induction of Labour: Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Labor, Induced
Keywords: Misoprostol
Labor, Obstetric
Labor, Induced
Lead sponsor: Instituto Materno Infantil Prof. Fernando Figueira
Sponsor class: OTHER
Collaborators: name: Instituto de Saúde Elpidio de Almeida
name: Universidade Federal do Ceara
First posted: 2009-10-09
Enrollment: 400
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Vaginal delivery
timeFrame: 24 hours
measure: Hyperstimulation syndrome
timeFrame: 24 hours
measure: Cesarean section
timeFrame: 3 days
measure: Severe neonatal morbidity or perinatal death
timeFrame: 28 days
measure: Serious maternal morbidity or maternal death
timeFrame: 42
Secondary outcomes:
measure: Need of oxytocin for augmentation of labour
timeFrame: 48 hours
measure: Number of doses needed to bring on labour
timeFrame: 48 hours
measure: Interval from 1st dose to labour
timeFrame: 48 hours
measure: Interval from 1st dose to delivery
timeFrame: 48 hours
measure: Failed induction
timeFrame: 72 hours
measure: Tachysystole
timeFrame: 48 hours
measure: Uterine rupture
timeFrame: 72 houras
measure: Need of labour analgesia
timeFrame: 48 hours
measure: Instrumental delivery
timeFrame: 48 hours
measure: Side effects: nausea, vomit, diarrhea, postpartum haemorrhage
timeFrame: 72 hours
measure: Maternal death
timeFrame: 42 days
measure: Meconium
timeFrame: 72 hours
measure: Non-reassuring fetal heart rate
timeFrame: 72 hours
measure: Apgar scores less than 7 at 1st and 5th minute
timeFrame: 1st and 5th minutes after delivery
measure: Admission at neonatal intensive care unit
timeFrame: 28 days
measure: Perinatal or neonatal death
timeFrame: 28 days
measure: Neonatal encephalopathy
timeFrame: 28 days
measure: Women not satisfied with route of drug administration
timeFrame: 48 hours after delivery
Other outcomes:
Locations:
city: Recife
country: Brazil
facility: Instituto de Medicina Integral Professor Fernando Figueira (IMIP)
state: Pernambuco
Study officials:
affiliation: Professor Fernando Figueira Integral Medicine Institute
name: Alex SR Souza, Phd student
role: STUDY_CHAIR
affiliation: Professor Fernando Figueira Integral Medicine Institute
name: Melania MR Amorim, Phd
role: STUDY_DIRECTOR
affiliation: Professor Fernando Figueira Integral Medicine Institute
name: Aurélio AR Costa, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Souza AS, Feitosa FE, Costa AA, Pereira AP, Carvalho AS, Paixao RM, Katz L, Amorim MM. Titrated oral misoprostol solution versus vaginal misoprostol for labor induction. Int J Gynaecol Obstet. 2013 Dec;123(3):207-12. doi: 10.1016/j.ijgo.2013.06.028. Epub 2013 Sep 3.
citation: Orange FA, Passini R Jr, Melo AS, Katz L, Coutinho IC, Amorim MM. Combined spinal-epidural anesthesia and non-pharmacological methods of pain relief during normal childbirth and maternal satisfaction: a randomized clinical trial. Rev Assoc Med Bras (1992). 2012 Jan-Feb;58(1):112-7.