Evaluation of Outpatient Versus Inpatient Induction of Labor Using Misoprostol: A Multicenter Randomized Controlled Trial

Trial ID: 2023-507164-39-00
Sponsor: Vaestra Goetalandsregionen

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Diseases & Conditions

Induced labour Labour induction

Objectives

The primary objective of this study is to evaluate whether **outpatient induction** of labor is as safe and effective as inpatient induction. This is clinically relevant as it could potentially offer a more flexible and less resource-intensive option for labor induction, which may benefit both healthcare systems and patients.

Secondary objectives include assessing the efficacy and healthcare costs associated with outpatient versus inpatient induction. This involves comparing the proportions of spontaneous and instrumental vaginal deliveries, the time to delivery within 24 and 48 hours, and the induction-to-delivery interval. Additionally, the study will evaluate total hospital hours, number of visits, telephone calls, need for ambulance transport, and the impact on subsequent pregnancies and delivery modes. Cost-effectiveness of outpatient induction compared to inpatient induction will also be analyzed. Furthermore, the study aims to assess the acceptability of outpatient versus inpatient induction among patients, partners, and healthcare staff, including their experiences and perceptions of the induction process in both settings.

Participants

The clinical trial focuses on the **induction of labour** and involves a study population exclusively composed of females aged 18 to 45 years. Participants are required to have an uncomplicated live singleton pregnancy, with gestational age ranging from 37+0 to 41+6 weeks, as determined by ultrasound measurements. The trial does not include male subjects. The selection criteria emphasize the ability of participants to reach the hospital within a reasonable time frame, communicate effectively with hospital staff, and present a stable cephalic presentation. The trial population is considered vulnerable, and the sponsor has not provided the total number of participants. Key lifestyle considerations, such as diet and physical activity, are not specified. The inclusion criteria are based on medical history and clinical examinations, ensuring participants have a normal CTG classification according to the antepartal Swedish Society of Obstetrics and Gynaecology criteria. The trial aims to assess the safety and effectiveness of outpatient versus inpatient induction.

Plans and Procedures

The clinical trial is designed to evaluate the safety and efficacy of **outpatient induction** of labor compared to inpatient induction. This is a multicenter, randomized, controlled trial with a double-blind design to ensure unbiased results. The trial is expected to run from December 1, 2021, to December 31, 2028. Participants will be women aged 18-45 years with an uncomplicated live singleton pregnancy, between 37+0 to 41+6 weeks of gestation, and a stable cephalic presentation. The primary endpoints include safety, defined as a composite outcome of severe perinatal morbidity or mortality, and efficacy, measured by the proportion of women achieving vaginal delivery.

Study visits will follow a structured sequence, beginning with an inclusion (screening) visit to assess eligibility based on medical history and clinical examination. This includes evaluating the **Bishop score** and conducting a **CTG scan**. Follow-up visits will monitor the induction process and collect data on delivery outcomes. The end-of-study visit will conclude the participant's involvement, ensuring all necessary data is collected and any adverse events are addressed. The expected length of participant involvement is up to two days, corresponding to the maximum treatment period with **misoprostol** tablets, administered orally.

Participants may be withdrawn from the study if they experience adverse reactions, fail to comply with the study protocol, or if the investigator deems it necessary for safety reasons. Secondary endpoints will explore pregnancy and delivery-related outcomes, including maternal and neonatal safety, as well as qualitative assessments of the experiences of women, partners, and healthcare staff. The trial will also assess cost-effectiveness and future pregnancy outcomes. The study aims to provide comprehensive data to inform clinical practice regarding the induction of labor in an outpatient setting.

Treatment

The clinical trial involves the use of **misoprostol** as the experimental medication. The pharmaceutical form of the medication is a tablet, marketed under the name Angusta 25 mikrogram tabletter. Each tablet contains 25 micrograms of the active substance, **misoprostol**, which is of chemical origin. The medication is administered orally. The maximum daily dose is 200 micrograms, and the total maximum dose over the treatment period is 400 micrograms. The treatment period is limited to a maximum of 2 days. The medication is manufactured by NORGINE B.V. and is not a pediatric formulation. Participant compliance with the dosing schedule will be monitored throughout the trial.

In this study, there are no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments mentioned. The primary objective of the trial is to evaluate the safety and effectiveness of outpatient induction compared to inpatient induction. The trial is designed as a multicenter randomized controlled trial, ensuring rigorous assessment of the treatment's efficacy and safety.

Efficacy

The efficacy of the clinical trial titled "OPTION – OutPatienT InductiON: Labour induction in an outpatient setting - a multicentre randomized controlled trial" will be assessed primarily by evaluating the proportion of women who achieve vaginal delivery. This primary endpoint is designed to determine the effectiveness of outpatient induction compared to inpatient induction. Secondary endpoints will include various pregnancy and delivery-related outcomes, such as the proportion of women who deliver vaginally within 24 or 48 hours from the start of induction. These outcomes will be obtained via registry data and are descriptive in nature.

Additional secondary endpoints will explore the experiences of women and their partners regarding self-efficacy, health-related quality of life, pain catastrophizing, anxiety, and depression. Qualitative interviews will be conducted to gather insights into the experiences of women and partners, including childhood experiences and levels of breastfeeding. The trial will also assess the understanding of healthcare staff's experiences with outpatient versus inpatient induction of low-risk pregnancies, as well as the cost-effectiveness and future pregnancy outcomes. The trial is set to conclude by December 31, 2028, with recruitment having started on December 1, 2021.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Based on medical history: women 18-45 years old
Based on medical history: able to communicate with the hospital
Based on medical history: uncomplicated live singleton pregnancy
Based on medical history: pregnancy week ≥37+0 to 41+6 according to crown rump length (CRL) or biparietal diameter (BPD<55 mm) at first or second trimester ultrasound
Based on medical history: Stable cephalic presentation
Based on clinical examination before start of induction including Leopold´s manoeuvres, digital cervical exam, abdominal ultrasound, blood pressure and CTG scan, if indicated temperature: Stable cephalic presentation.
Based on clinical examination before start of induction including Leopold´s manoeuvres, digital cervical exam, abdominal ultrasound, blood pressure and CTG scan, if indicated temperature: Bishop score <6
Based on clinical examination before start of induction including Leopold´s manoeuvres, digital cervical exam, abdominal ultrasound, blood pressure and CTG scan, if indicated temperature: CTG classified as normal according to the antepartal Swedish Society of Obstetrics and Gynaecology (Svensk Förening för Obstetrik och Gynekologi, SFOG) criteria (www.ctgutbildning.se)
Based on observation the first 45 min after start of induction: in case of induction with catheter method: CTG classified as normal according to the antepartal Swedish Society of Obstetrics and Gynaecology (Svensk Förening för Obstetrik och Gynekologi, SFOG) criteria (www.ctgutbildning.se)
Based on medical history: Able to reach the hospital in a reasonable time, at the discretion of the investigator with a maximum of 60 min as a benchmark

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Exclusion Criteria

Based on medical history: previous uterine surgery with uterine scar, e.g. caesarean section or myomectomy
Based on medical history: Known small for gestational age (SGA) defined as <2 standard deviations according to Marsal et al or intrauterine growth restriction (IUGR)
Based on medical history: known allergy to any of the components of the balloon catheter or Angusta® (for the respective method only)
Based on clinical examination before start of induction including Leopold´s manoeuvres, digital cervical exam, abdominal ultrasound, blood pressure and CTG scan, if indicated temperature: If the criteria outlined below are not met in their respective situation, the patient shall be excluded from the study: 1) In case of late term ≥41+0 to 41+6 weeks abdominal ultrasound will be performed and mean abdominal diameter (MAD) must be ≥110 mm. In case MAD <110 mm, the foetal weight will be estimated to exclude SGA foetus defined as <2 standard deviations according to Marsal et al the patient should be excluded. 2) In case of dietary or metformin treated gestational diabetes foetal weight to be or have been estimated by abdominal ultrasound within the last three weeks before induction and the result needs to be within normal range. 3) In case of stable hypertension foetal weight needs to be estimated by abdominal ultrasound within the last two weeks before induction and showing no SGA/IUGR foetus. 4) In case of indication for induction being prolonged latent phase, maternal age, mild intrahepatic cholestasis, pelvic girdle pain, PROM or psychosocial, a normal fundal height measurement according to the Swedish reference curves must be normal. In case of not-normal fundal height measurement: foetal weight estimation must be performed and showing no SGA/IUGR. 5) For all other indications foetal weight is estimated by abdominal ultrasound at the discretion of the investigator.
Based on clinical examination before start of induction including Leopold´s manoeuvres, digital cervical exam, abdominal ultrasound, blood pressure and CTG scan, if indicated temperature: Oligohydramniosis: deepest vertical pocket <20 mm or amniotic fluid index <50 mm
Based on clinical examination before start of induction including Leopold´s manoeuvres, digital cervical exam, abdominal ultrasound, blood pressure and CTG scan, if indicated temperature: polyhydramniosis: amniotic fluid index >250 mm
Based on clinical examination before start of induction including Leopold´s manoeuvres, digital cervical exam, abdominal ultrasound, blood pressure and CTG scan, if indicated temperature: maternal pyrexia ≥38°C
Based on clinical examination before start of induction including Leopold´s manoeuvres, digital cervical exam, abdominal ultrasound, blood pressure and CTG scan, if indicated temperature: known low-lying placenta (less than 20 mm from internal os measured by ultrasound)
Based on clinical examination before start of induction including Leopold´s manoeuvres, digital cervical exam, abdominal ultrasound, blood pressure and CTG scan, if indicated temperature: Regarding premature rupture of membranes (PROM): 1) PROM is exclusion criteria for catheter method 2) PROM is exclusion criteria for prostaglandin method if: 2.1) Time point for confirmed PROM with timepoint for PROM as indicated by the woman >48 hours. 2.2) Known colonisation with group B streptococci or previous pregnancy complication linked to group B streptococci
Based on medical history: pregestational (diagnosis before pregnancy or before gestational week 25) or insulin treated gestational diabetes
Based on observation the first 45 min after start of induction: any adverse events within the first 45 min after start of induction, e.g. heavy bleeding, pain, PROM in case PROM was not indication for induction of labour
Based on observation the first 45 min after start of induction: start of contractions
Based on medical history: dietary or metformin treated gestational diabetes with small or large for gestational age foetus
Based on medical history: preeclampsia or instable hypertensive disease
Based on medical history: Intrahepatic cholestasis with serum bile acids ≥40 µmol/L
Based on medical history: intrauterine foetal death (IUFD) in previous pregnancy
Based on medical history: known foetal malformations or other foetal condition affecting the delivery or immediate care of the new-born
Based on medical history: congenital uterine malformation which may affect safety
Based on medical history: other condition requiring inpatient care, e.g. delivery within 60 min from arriving at the hospital in previous pregnancy
Based on clinical examination before start of induction including Leopold´s manoeuvres, digital cervical exam, abdominal ultrasound, blood pressure and CTG scan, if indicated temperature: • Small for gestational age (SGA) defined as <2 and in case of diabetes either large for gestational age (LGA) defined as >2 standard deviation according to Marsal et al or suspected growth acceleration.