Oral Titrated Misoprostol for Induction of Labour (OTISMISO)

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 Overview

• Status: Completed
• Conditions: Labor, Induced
• Intervention / Treatment: Drug: Misoprostol; Drug: Misoprostol

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.

• Study Type: Interventional
• Enrollment (Anticipated): 400
• Phase: Not Applicable

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: 18 years to 50 years (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:

• 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

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: Oral Titrated Misoprostol Solution	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.; Other Names: Cytotec; Prostokos; Drug: Misoprostol; Vaginal tablets will have 25mcg of misoprostol or placebo.; Other Names: Cytotec; Prostokos
Active Comparator: Vaginal Misoprostol	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.; Other Names: Cytotec; Prostokos; Drug: Misoprostol; Vaginal tablets will have 25mcg of misoprostol or placebo.; Other Names: Cytotec; Prostokos

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Instituto Materno Infantil Prof. Fernando Figueira
• Collaborators: Universidade Federal do Ceara; Instituto de Saúde Elpidio de Almeida
• Investigators: Study Chair: Alex SR Souza, Phd student, Professor Fernando Figueira Integral Medicine Institute; Study Director: Melania MR Amorim, Phd, Professor Fernando Figueira Integral Medicine Institute; Principal Investigator: Aurélio AR Costa, PhD, Professor Fernando Figueira Integral Medicine Institute

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: October 8, 2009
• First Submitted That Met QC Criteria: October 8, 2009
• First Posted (Estimate): October 9, 2009

Study Record Updates

• Last Update Posted (Estimate): June 23, 2011
• Last Update Submitted That Met QC Criteria: June 22, 2011
• Last Verified: October 1, 2009

More Information

Terms related to this study

• Keywords: Misoprostol; Labor, Obstetric; Labor, 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: ORALTIMI