Outpatient Induction of Labor With Oral Misoprostol

Outpatient Induction of Labor With Oral Misoprostol: A Multicenter Randomized-controlled Trial

Induction of labor is an increasingly used intervention in obstetrics due to expanding indications, which more often includes relatively healthy women with uncomplicated pregnancies. While induction of labor traditionally is offered in an inpatient setting, a shift towards an outpatient setting is increasing despite insufficient evidence regarding safety and effectiveness. Oral misoprostol is easy for the pregnant women to administer and the risk of uterine hyperstimulation with fetal heart rate changes is found to be low. Strong evidence concludes that oral misoprostol is preferable as an induction agent and is recommended by the World Health Organization (WHO).

The investigators will perform a multicenter randomized-controlled trial comparing labor induction in an outpatient versus inpatient setting, aiming to increase knowledge on outpatient induction of labor with oral misoprostol. The study is based on experiences and findings from a recently performed pilot trial and targets a large group of relatively healthy pregnant women where induction of labor is decided.

The investigators hypothesize that women induced in an outpatient setting will be more satisfied than women induced in an inpatient setting.

Study Overview

• Status: Completed
• Conditions: Induction of Labor
• Intervention / Treatment: Other: Inpatient setting; Other: Outpatient setting

Detailed Description

After induction of labor is decided the women will be recruited according to inclusion and exclusion criteria's.

The inpatient induction group will receive the following treatment:

Oral misoprostol 25ug every two hours and a cardiotocography for fetal monitoring every 4-6 hours until start of contractions, the next 48 hours while admitted to the maternity ward. The participating women will be transferred to the labor ward by start of contractions or need for closer fetal surveillance and/or analgesia.

The outpatient induction group will receive the following treatment:

These participating women receive the first oral misoprostol 25ug at the maternity unit. After two hours if the cardiotocograph is normal and there are no signs of contractions, these women go home. At home, the women will continue to take 25ug misoprostol every two hours until 22 pm or until the contractions begin. Maximum time spent at home is 48 hours and maximum number of tablets is 12 during this period (6 tablets each day). The women will also receive oral and written information regarding when to return to the maternity ward. Information sheets for the midwives and included women will be adapted from those used in the pilot study.

If the contractions are still absent after 48 hours or a maximum of 12 tablets (6 per day), all women (both inpatient and outpatient) are admitted to the maternity ward for further induction of labor. All women will receive equal standard of care including fetal surveillance after admittance to the hospital. Further follow up is in accordance with standard procedure of the maternity ward. Questions about fidelity to the proposed protocol across sites will be asked in the patient questionnaire.

• Study Type: Interventional
• Enrollment (Actual): 302
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Janne Rossen, MD, PhD; Phone Number: +47 38076266; Email: janne.rossen@sshf.no
• Study Contact Backup: Name: Fride E Austad, MD; Email: fride.efjestad.austad@sshf.no

Study Locations

• Norway
  • Bergen, Norway
    • Haukeland University Hospital
  • Bodø, Norway
    • Nordlandssykehuset HF
  • Fredrikstad, Norway
    • Østfold Hospital Trust
  • Kristiansand, Norway, 4604
    • Sorlandet Hospital Trust
  • Trondheim, Norway
    • St. Olavs Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ≥ 37 gestational weeks, vertex presentation, single pregnancy
• Age ≥ 18 years
• Understand and read Norwegian
• Distance to hospital less than 1 hour

• Normal ultrasound including:

  • fetal movements
  • amniotic fluid (deepest single vertical pocket) > 2 cm
  • estimated fetal weight ≥ -15% (≥ 10 percentile)
• Normal antenatal cardiotocography
• Women with stable hypertension and uncomplicated preeclampsia without indication for inpatient treatment can be included after individual assessment.
• Access to partner or contact person at home for transportation to hospital

Exclusion Criteria:

• Premature rupture of membranes
• Uterine scar
• BMI ≥ 40
• Abnormal fetal Doppler (if examined); umbilical artery pulsatility index ≥ 95 percentile and/or cerebroplacental ratio <1
• Fetal anomaly or chromosomic / genetic disorder
• Grand multipara (P≥4)
• Cognitive barriers
• Pregnancy complications such as preeclampsia requiring in-hospital treatment, insulin dependent diabetes or other conditions associated with risk of fetal hypoxia during labor
• Signs of infection or serious health problems
• Favorable cervix and / or previous obstetric history providing contraindications for induction with misoprostol
• Combined risk factors, individually evaluated by the attending obstetrician

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Induction of labour with oral misoprostol, inpatient setting; These women receive all treatment in the maternity unit.	Other: Inpatient setting; These women stay at the maternity unit
Experimental: Induction of labour with oral misoprostol, outpatient setting; These women are observed 2 hours after they receive one dose of oral misoprostol before they leave the maternity unit.	Other: Outpatient setting; These women leave the maternity unit

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal childbirth experience and maternal experience with induction of labor	The women will answer electronic questionaires at inclusion and postpartum	up to 12 days after delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Labor outcomes	Hours from start induction and start active labor	From 1 hour to average of 48 hours
Cost per delivery	We will calculate the differences of costs and effects of one or more alternatives, and present the differences in the form of a ratio (ICER), i.e. the cost per unit of health outcome or effect. We will calculate cost-effectiveness (δ costs / δ effects) to evaluate whether outpatient induction shows to be dominant strategy regarding patient satisfaction.	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Sorlandet Hospital HF
• Collaborators: Ostfold Hospital Trust; Haukeland University Hospital; St. Olavs Hospital; Nordlandssykehuset HF
• Investigators: Principal Investigator: Janne Rossen, MD, PhD, Sorlandet HF

Publications and helpful links

General Publications

• WHO recommendations: Induction of labour at or beyond term. Geneva: World Health Organization; 2018. Available from http://www.ncbi.nlm.nih.gov/books/NBK535795/
• Alfirevic Z, Gyte GM, Nogueira Pileggi V, Plachcinski R, Osoti AO, Finucane EM. Home versus inpatient induction of labour for improving birth outcomes. Cochrane Database Syst Rev. 2020 Aug 27;8(8):CD007372. doi: 10.1002/14651858.CD007372.pub4.
• Alfirevic Z, Aflaifel N, Weeks A. Oral misoprostol for induction of labour. Cochrane Database Syst Rev. 2014 Jun 13;2014(6):CD001338. doi: 10.1002/14651858.CD001338.pub3.
• McDonagh M, Skelly AC, Tilden E, Brodt ED, Dana T, Hart E, Kantner SN, Fu R, Hermesch AC. Outpatient Cervical Ripening: A Systematic Review and Meta-analysis. Obstet Gynecol. 2021 Jun 1;137(6):1091-1101. doi: 10.1097/AOG.0000000000004382.
• Helmig RB, Hvidman LE. An audit of oral administration of Angusta(R) (misoprostol) 25 microg for induction of labor in 976 consecutive women with a singleton pregnancy in a university hospital in Denmark. Acta Obstet Gynecol Scand. 2020 Oct;99(10):1396-1402. doi: 10.1111/aogs.13876. Epub 2020 May 19.
• Ten Eikelder ML, Oude Rengerink K, Jozwiak M, de Leeuw JW, de Graaf IM, van Pampus MG, Holswilder M, Oudijk MA, van Baaren GJ, Pernet PJ, Bax C, van Unnik GA, Martens G, Porath M, van Vliet H, Rijnders RJ, Feitsma AH, Roumen FJ, van Loon AJ, Versendaal H, Weinans MJ, Woiski M, van Beek E, Hermsen B, Mol BW, Bloemenkamp KW. Induction of labour at term with oral misoprostol versus a Foley catheter (PROBAAT-II): a multicentre randomised controlled non-inferiority trial. Lancet. 2016 Apr 16;387(10028):1619-28. doi: 10.1016/S0140-6736(16)00084-2. Epub 2016 Feb 3.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Actual): March 29, 2023
• Study Completion (Actual): April 29, 2023

Study Registration Dates

• First Submitted: November 3, 2021
• First Submitted That Met QC Criteria: November 22, 2021
• First Posted (Actual): December 3, 2021

Study Record Updates

• Last Update Posted (Actual): October 24, 2023
• Last Update Submitted That Met QC Criteria: October 23, 2023
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: outpatient; misoprostol; induction; childbirth experience
• Other Study ID Numbers: 261787/2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No