Clinical trial NCT05857059: Misoprostol for Induction of Labor in Obese Women: Comparison Between 25 and 50 mcg Oral Administration
Official title: Misoprostol for Induction of Labor in Obese Women: Comparison Between 25 and 50 mcg Oral Administration - a Randomized Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Labor, Induced
Obesity
Pregnancy
Cesarean Section
Lead sponsor: Centro Hospitalar e Universitário de Coimbra, E.P.E.
Sponsor class: OTHER
First posted: 2023-05-12
Enrollment: 228
Sex: FEMALE
Minimum age (years): 15
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Pregnant women seen at the obstetric clinic of Maternidade Daniel de Matos, with a first trimester ultrasound pregnancy dating at our institution; with a maternal BMI measurement in the first trimester ≥ 30 kg/m2 and with a maternal or obstetric indication for IOL, who agreed to participate in the study. They will be randomized into two groups: one will consist of pregnant women undergoing the basic IOL protocol of Maternidade Daniel de Matos (oral misoprostol 25µcg every 2 hours); the other will be submitted to a 50µcg dosage every 2 hours, maximum of 7 doses per day (maximum 2 days). The pregnant woman will have a choice of an envelope, which will be her group assignment and will be coded until the end of the trial.
Primary purpose: TREATMENT

Brief summary: In recent decades, obesity has become a prevalent issue in Portugal, with 38.6% and 13.8% of the population being overweight or obese, respectively. Obese pregnant women have a higher rate of obstetric complications, including hypertensive complications, gestational diabetes and fetal macrosomia, leading to increased induction of labor (IOL) and cesarean section (CS) rates. To determine the effect of increasing oral misoprostol dose on CS rate in obese pregnant women undergoing IOL, a randomized controlled trial with a sample size of 114 cases in each group was calculated to detect a 15% difference in CS rate. The primary objective is to determine the effect of increasing oral misoprostol dose, with secondary goals being to compare successful IOL rates and their relationship with oral misoprostol dose, as well as to evaluate tolerability and side effects in relation to different doses of oral misoprostol.

Detailed description: The prevalence of obesity has increased dramatically in recent decades, with implications for women of reproductive age and changes in obstetric and perinatal outcomes. In Portugal, it is estimated that 38.6 per cent and 13.8 per cent of the population are overweight or obese, respectively. Compared with women of normal weight, obese pregnant women have a higher rate of obstetric complications. These include hypertensive complications, gestational diabetes and fetal macrosomia. These factors lead to an increased need for IOL before the end of the pregnancy and, consequently, to a reduced degree of cervical dilatation prior to IOL. In addition, the above-mentioned co-morbidities are associated with a higher rate of CS. For all these reasons, obese women have higher IOL and CS rates. The literature also confirms that the degree of obesity is directly related to IOL failure. In some studies, the rate of failed induction is 20.2% and 24.2% in women with obesity grades I and II, respectively. However, few studies have been conducted to determine which IOL agents most commonly induce vaginal labour in obese women, and no studies have defined the most appropriate dose for maternal BMI.

This study provides a breakthrough in understanding the mechanism of labour and response to misoprostol in obese women, as there is a lack of prospective human studies in this area.

Sample size calculation was based on CS rate in obese versus non-obese groups as the primary outcome. According to previous studies, a 22% CS rate in non-obese pregnant women undergoing IOL was calculated, with a between-groups difference of 15% on CS rates being considered clinically significant. Therefore, we set the power at 80%, the alpha error at 0.05 and the ratio of the two study groups at 1:1. Accordingly, 114 cases were needed in each group to detect 15% difference in CS rate.

Primary objective: To determine the effect of increasing oral misoprostol dose on CS rate in obese pregnant women undergoing IOL.

Secondary goals: Comparison of successful IOL rates and their relationship with oral misoprostol dose. Evaluation of tolerability and side effects in relation to different doses of oral misoprostol.

Eligibility criteria: Inclusion Criteria:

* BMI ≥ 30 kg/m2 recorded based on maternal weight at preconception or in the first trimester
* Singleton live gestation with vertex presentation
* Pregnancies followed in our institution with sonographic confirmation of gestational age in the first trimester
* Obstetrical indication for labor induction
* Bishop score of \<5 at the time of induction of labor

Exclusion Criteria:

* Underweight and normal weight women (BMI \<30 kg/m2)
* Known hypersensitivity to prostaglandins
* Preterm gestations (\< 37 weeks)
* Multiple gestation
* Women who cannot give their informed consent
* Contraindications for vaginal delivery
* Previous c-section or uterine scar due to previous gynecological surgery
* Maternal or fetal pathology (for example: fetal indications: non-reassuring fetal status - intra-uterine growth restriction with abnormal umbilical doppler, abnormal fetal cardiac rhythm; stillbirth; or maternal/pregnancy related indications such as placenta previa)

Primary outcomes:
measure: Cesarean section rates
timeFrame: Up to 3 days after first misoprostol intake until delivery (vaginal or cesarean section)
measure: Indication for cesarean section
timeFrame: Delivery
Secondary outcomes:
measure: Rate of vaginal delivery within 24 hours
timeFrame: Time of first misoprostol intake until vaginal delivery
measure: Time interval from the first dose of misoprostol to vaginal delivery
timeFrame: Time of first misoprostol intake until vaginal delivery
measure: Rate of instrumental delivery
timeFrame: Delivery
measure: Time interval from the first dose of misoprostol to cesarean section delivery
timeFrame: Time of first misoprostol intake until cesarean section delivery
measure: Incidence of misoprostol adverse effects
timeFrame: Time of first misoprostol intake until vaginal or cesarean section delivery
Other outcomes:
Locations:
city: Coimbra
country: Portugal
facility: Iolanda João Mora Cruz de Freitas Ferreira
Study officials:
References: