Sublingual Misoprostol for Induction of Labor (SUBMISO)

Sublingual Misoprostol 12,5 mcg Versus Vaginal Misoprostol 25 mcg for Induction of Labour of Alive and Term Fetus : Randomized Controlled Trial

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.

Study Overview

• Status: Completed
• Conditions: Labor; Induced
• Intervention / Treatment: Drug: Sublingual Misoprostol; Drug: Misoprostol 25mcg

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 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.

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • Pernambuco
    • Recife, Pernambuco, Brazil, 50070-550
      • Instituto de Medicina Integral Professor Fernando Figueira (IMIP)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sublingual Misoprostol 12,5mcg; Sublingual misoprostol or placebo tablete will be administered for each six hours until the maximum dose of 100mcg or eight tablets.	Drug: Sublingual Misoprostol; Sublingual misoprostol or placebo tablets will be administered for each six hours until the maximum dose of 100mcg or eight tablets; Other Names: Cytotec; Prostokos
Active Comparator: Vaginal Misoprostol 25 mcg; 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; Vaginal misoprostol or placebo tablets will be administered for each six hours until the maximum dose of 200mcg or eight tablets.; Other Names: Prostokos Cytotec

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Professor Fernando Figueira Integral Medicine Institute
• Collaborators: Maternidade Escola Assis Chateaubriand

Publications and helpful links

General Publications

• Gattas DSMB, de Amorim MMR, Feitosa FEL, da Silva-Junior JR, Ribeiro LCG, Souza GFA, Souza ASR. Misoprostol administered sublingually at a dose of 12.5 mug versus vaginally at a dose of 25 mug for the induction of full-term labor: a randomized controlled trial. Reprod Health. 2020 Apr 10;17(1):47. doi: 10.1186/s12978-020-0901-8.
• Gattas DSMB, da Silva Junior JR, Souza ASR, Feitosa FE, de Amorim MMR. Misoprostol administered sublingually at a dose of 12.5 mug versus vaginally at a dose of 25 mug for the induction of full-term labor: a randomized controlled trial protocol. Reprod Health. 2018 Apr 18;15(1):65. doi: 10.1186/s12978-018-0508-5.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2014
• Primary Completion (Actual): November 30, 2016
• Study Completion (Actual): November 30, 2016

Study Registration Dates

• First Submitted: July 29, 2011
• First Submitted That Met QC Criteria: July 29, 2011
• First Posted (Estimate): August 1, 2011

Study Record Updates

• Last Update Posted (Actual): September 18, 2019
• Last Update Submitted That Met QC Criteria: September 15, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Labor; Misoprostol; Sublingual; Induced
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Gastrointestinal Agents; Reproductive Control Agents; Anti-Ulcer Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Oxytocics; Misoprostol
• Other Study ID Numbers: SUBMISO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Sharing Time Frame: After publication in scientific journal
• IPD Sharing Supporting Information Type: Study Protocol