Comparison of Cook's Balloon and Dinoprostone for Labor Induction in Term Pregnancies with Fetal Growth Restriction: A Randomized Controlled Trial

The primary objective of this study is to evaluate whether **cervical ripening** with a Cook's balloon for the induction of labor from week 37 + 0 of gestation in cases of late **intrauterine growth restriction** increases the probability of vaginal delivery compared to the use of vaginal **dinoprostone**, without increasing neonatal morbidity. This is clinically relevant as it aims to improve delivery outcomes in pregnancies complicated by fetal growth restriction, potentially reducing the need for cesarean sections and associated maternal and neonatal risks.

Secondary objectives include:

• Comparing the percentage of cesarean sections performed due to suspected loss of fetal well-being.
• Studying the duration between the initiation of cervical ripening and the time of delivery.
• Analyzing neonatal outcomes, including neonatal acidosis, the MAIN score for neonatal morbidity, and admissions to the Neonatal Intensive Care Unit.

The clinical trial focuses on a study population consisting exclusively of **female** participants, as the condition under investigation pertains to **fetal growth restriction**. The trial does not include male subjects, and the population is not considered vulnerable. Participants are required to be at least 18 years of age, with a gestational age of 37 weeks or more, as determined by a first-trimester ultrasound. The trial targets individuals with a single gestation and cephalic presentation, who meet specific criteria for Stage I intrauterine growth restriction. These criteria include an estimated fetal weight below the 3rd percentile or below the 10th percentile with additional indicators such as an umbilical artery pulsatility index above the 95th percentile or a cerebro-placental index below the 5th percentile. Participants must have a Bishop score of less than 7, an intact amniotic sac, no previous cesarean section, and no contraindications for vaginal delivery or labor induction. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the efficacy of cervical ripening using a Cook's balloon compared to **dinoprostone** for labor induction in term pregnancies complicated by fetal growth restriction. This study is a randomized, controlled trial with a double-blind design to ensure unbiased results. The trial is expected to run from March 21, 2023, to March 31, 2025, with participant involvement lasting until the end of the study or until early termination criteria are met.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as single gestation, age of 18 years or older, gestational age of at least 37 weeks, cephalic presentation, and specific fetal growth restriction parameters. Following successful screening, participants will be randomized to receive either the Cook's balloon or vaginal **dinoprostone**. The primary endpoint is the achievement of vaginal delivery, with secondary endpoints focusing on neonatal morbidity.

Follow-up visits will be scheduled to monitor the progress of labor induction and assess any adverse events. The end-of-study visit will occur after delivery to evaluate the outcomes and collect final data. Participants may be withdrawn from the study if they experience any contraindications for vaginal delivery, develop conditions that necessitate cesarean delivery, or if they choose to withdraw consent. The trial aims to provide valuable insights into the optimal method for labor induction in cases of fetal growth restriction, with the goal of improving maternal and neonatal outcomes.

The clinical trial involves the use of **dinoprostone** as the experimental medication. The product utilized is "PROPESS 10 mg sistema de liberación vaginal," which is a **vaginal delivery system**. The active substance, **dinoprostone**, is of chemical origin and is administered via vaginal use. The dosage form is designed to release 10 mg of **dinoprostone**. The maximum daily dose and the total dose are both set at 20 mg, with a maximum treatment period of one day. The administration of the medication is monitored to ensure compliance with the dosing schedule.

In addition to the experimental treatment, the study includes a comparator treatment using a Cook's balloon for cervical ripening. This non-experimental treatment is employed to induce labor in term pregnancies with fetal growth restriction. The objective is to compare the efficacy of the Cook's balloon with the vaginal **dinoprostone** in increasing the probability of vaginal delivery without elevating neonatal morbidity. The study does not involve the use of a placebo, and the comparator treatment serves as the standard-of-care therapy in this context.

The efficacy of the clinical trial titled "Cook's balloon versus dinoprostone for Labor Induction of term pregnancies with fetal GROWth restriction (COLIGROW study)" will be assessed primarily through the endpoint of vaginal delivery, recorded as a binary outcome (yes/no). The trial aims to evaluate whether cervical ripening with a Cook's balloon increases the probability of vaginal delivery compared to the use of vaginal **dinoprostone** in pregnancies affected by late intrauterine growth restriction, without increasing neonatal morbidity. The primary endpoint will be measured at the time of delivery, following the induction of labor from week 37 + 0 of gestation. The trial is designed as a low-intervention study, utilizing an authorized investigational medicinal product in accordance with its marketing authorization. The study will adhere to the specified inclusion criteria, ensuring that participants meet the necessary conditions for trial eligibility, such as gestational age and fetal growth parameters.