OBJECTIVE: The purpose of this study was to identify the maximum tolerable dose and to determine the efficacy of different misoprostol dose reservoirs in an intravaginal controlled-release hydrogel polymer. STUDY DESIGN: Nulliparous women at > or = 37 weeks' gestation requiring cervical ripening and induction of labor were treated with misoprostol in a controlled-release, retrievable hydrogel polymer vaginal insert. Sequential cohorts of 6 patients were to be treated with escalating dose reservoirs of 25, 50, 100, 200, and 300 mug. The insert was to be removed upon onset of active labor, at 24 hours, or earlier if treatment-related adverse events occurred. The safety end point was determination of the maximum tolerable dose (MTD) based on occurrence of hyperstimulation syndrome. Our primary efficacy end point was time to vaginal delivery. RESULTS: Increasing reservoir doses of misoprostol up to 100 microg produced more rapid increases in modified Bishop scores, less need for oxytocin, and a shorter time to vaginal delivery. Doses above 100 microg did not further enhance cervical ripening or shorten time to vaginal delivery. The median time to vaginal delivery was 14.2 hours using the 100 microg dose. Uterine hyperstimulation and adverse fetal heart rate effects occurred with the 200 and 300 microg inserts. CONCLUSION: The 100 microg vaginal insert resulted in successful cervical ripening and rapid vaginal delivery with an acceptable safety profile for future randomized clinical trials.
OBJECTIVE: The purpose of this study was to identify the maximum tolerable dose and to determine the efficacy of different misoprostol dose reservoirs in an intravaginal controlled-release hydrogel polymer. STUDY DESIGN: Nulliparous women at > or = 37 weeks' gestation requiring cervical ripening and induction of labor were treated with misoprostol in a controlled-release, retrievable hydrogel polymer vaginal insert. Sequential cohorts of 6 patients were to be treated with escalating dose reservoirs of 25, 50, 100, 200, and 300 mug. The insert was to be removed upon onset of active labor, at 24 hours, or earlier if treatment-related adverse events occurred. The safety end point was determination of the maximum tolerable dose (MTD) based on occurrence of hyperstimulation syndrome. Our primary efficacy end point was time to vaginal delivery. RESULTS: Increasing reservoir doses of misoprostol up to 100 microg produced more rapid increases in modified Bishop scores, less need for oxytocin, and a shorter time to vaginal delivery. Doses above 100 microg did not further enhance cervical ripening or shorten time to vaginal delivery. The median time to vaginal delivery was 14.2 hours using the 100 microg dose. Uterine hyperstimulation and adverse fetal heart rate effects occurred with the 200 and 300 microg inserts. CONCLUSION: The 100 microg vaginal insert resulted in successful cervical ripening and rapid vaginal delivery with an acceptable safety profile for future randomized clinical trials.