Randomized Open‑Label Trial of Oral Misoprostol Combined with Osmotic Dilators Versus Sequential Misoprostol for Labour Induction in Women with Unprepared Cervix

The primary objective is to demonstrate that concurrent oral misoprostol administration with osmotic dilators reduces the total misoprostol dose compared with sequential administration for labour induction in women with an unprepared cervix, thereby potentially minimizing drug exposure while maintaining effective cervical ripening.

Secondary objectives include:

• Describe drug exposure and safety in both treatment arms.
• Compare impact on perinatal outcomes between the two regimens.
• Assess differences in labour duration and length of hospital stay.
• Evaluate the success rate of labour induction.

The sponsor did not provide this information. Participants were adult women (≥ 18 years) identified for labour induction at a gestational age of 38 + 0 to 41 + 6 weeks, with an unprepared cervix defined by a Bishop score < 6. Eligible subjects had a singleton, live fetus in cephalic presentation, physiological cardiotocography results, and provided signed informed consent. The trial population comprised pregnant females considered a vulnerable group, and enrollment was limited to patients meeting the principal inclusion criteria; no additional lifestyle or health status details were specified.

The OPTIMISO trial is a randomized, open‑label, controlled study evaluating two regimens for labour induction using oral misoprostol in women with an unprepared cervix. Eligible participants are women ≥18 years, singleton, cephalic pregnancy at 38 + 0 to 41 + 6 weeks, Bishop score <6, with a live fetus and signed informed consent. After a screening visit confirming eligibility, participants are randomly assigned to either a concurrent arm (oral misoprostol combined with osmotic dilators) or a sequential arm (osmotic dilators followed by oral misoprostol). The study period for each participant begins at the induction start and continues through labour, delivery, and discharge, with follow‑up assessments on the day of induction, during active labour, and at an end‑of‑study visit performed at hospital discharge. The primary endpoint is reduction of total misoprostol dose in the concurrent arm versus the sequential arm; secondary endpoints include number of doses, incidence of adverse events, maternal, labour, and neonatal outcomes, and various time intervals related to induction and delivery. Participant involvement typically spans from the screening visit to discharge, ranging from a few days to approximately one week. Recruitment is planned from April 2026 to September 2028, defining the overall trial duration.

The investigational product is Angusta 25 µg tablets containing misoprostol. The tablets are supplied in oral form. Each tablet provides 25 µg of the active substance, and a total dose of 200 µg is administered per the study protocol. The medication is taken by mouth according to the dosing schedule defined in the protocol.

Standard‑of‑care therapy in the trial includes the use of osmotic cervical dilators. These devices are inserted vaginally to facilitate cervical ripening prior to labour induction. Their use follows routine clinical practice and is applied in conjunction with the study medication as specified.

Drug administration is recorded in the trial case report form. Dosing times are documented, and compliance is assessed by pill count and patient diary entries. Any deviations from the prescribed schedule are reported to the study monitor.

The primary efficacy parameter is the reduction of the total misoprostol dose in the concurrent administration arm compared with the sequential arm, calculated by summing all oral misoprostol doses administered from induction start until delivery.

Secondary efficacy parameters comprise the number of misoprostol doses, incidence of adverse events related to misoprostol or osmotic dilators, maternal outcomes (uterine tachysystole, uterine rupture, severe perineal trauma, blood loss ≥ 1000 mL, infection complications, maternal mortality), labour outcomes (proportion of vaginal deliveries, assisted vaginal extractions, cesarean sections overall and for specific indications, manual placental removal, oxytocin use, epidural analgesia use), fetal/neonatal outcomes (including perinatal mortality, Apgar score at 1, 5 and 10 minutes, birth weight, umbilical artery pH and base excess, infectious complications, neonatal seizures, NICU admission within 24 hours, neonatal mortality), and timing measures (duration of induction, first‑stage and second‑stage labour, time from induction start to birth, length of hospital stay). Additional efficacy measures include rates of successful induction on the first and second attempts, need for induction retrial, and overall induction failure.

All efficacy endpoints will be recorded prospectively at predefined timepoints: at induction start, at onset of the first stage of labour, at delivery, and at discharge. Data will be entered into the trial database and analyzed according to the statistical analysis plan, with comparisons made between the concurrent and sequential treatment arms for each endpoint.