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Published on: June 6, 2020
Outpatient cervical ripening by nitric oxide donors for prolonged pregnancy: a randomized controlled trial
Thomas Schmitz1, Florent Fuchs, Emmanuel Closset
1Assistance Publique-Hôpitaux de Paris, Service de Gynécologie Obstétrique, Hôpital Robert Debré, Hôpital Bichat, Hôpital Saint-Antoine, and Hôpital Saint Vincent-de-Paul, Assistance Publique-Hôpitaux de Paris, Maternité Port-Royal, Université Paris Diderot, Université Pierre et Marie Curie, Université René Descartes, and INSERM UMR 1153 Equipe EPOPé, Paris, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Service de Gynécologie Obstétrique and Université Paris Sud, Le Kremlin-Bicêtre, Hôpital Jeanne de Flandre and Université Lille 2, Lille, Hôpital de Poissy Saint-Germain, Département de Gynécologie Obstétrique, Poissy, Université Versailles Saint-Quentin, Saint-Quentin en Yvelines, CHU de Nantes, Hôpital Mère Enfant, Service de Gynécologie Obstétrique, and Université de Nantes, Nantes, CHRU Bretonneau, Centre Olympe de Gouges, and Université François Rabelais, Tours, and CHU de Rouen, Service de Gynécologie Obstétrique, and Université de Rouen, Rouen, France.
Objective:
To assess whether outpatient cervical ripening at 41 0/7 weeks of gestation with the nitric oxide donor isosorbide mononitrate reduces cesarean delivery rates in nulliparous women with an unfavorable cervix.
Methods:
We recruited nulliparous pregnant women with a Bishop score less than 6 in a randomized, multicenter, double-blind, placebo-controlled trial. Women received 40 mg vaginal isosorbide mononitrate or a placebo at 41 0/7, 41 2/7, and 41 4/7 weeks of gestation. They returned home between visits. At 41 5/7 weeks of gestation, for women who had not yet given birth, labor was induced with oxytocin or prostaglandins, depending on cervical status. We needed 685 women per group to detect a 25% reduction in the cesarean delivery rate, the primary outcome measure, from 25% in the placebo group to 18.75% in the isosorbide mononitrate group (1-β=0.8, α=0.05, two-sided).
Results:
The NOCETER (NO donors for reduction of CEsareans at TERm) trial was a negative study. The cesarean delivery rate was 27.3% (185/678) in the isosorbide mononitrate group and 27.2% (186/684) in the placebo group (relative risk 1.00, 95% confidence interval [CI] 0.84-1.19). None of the maternal secondary efficacy outcomes differed between groups. Side effects were more common among women receiving isosorbide mononitrate than in the placebo group (78.8% [534/678] compared with 27.9% [191/684], relative risk 2.82, 95% CI 2.49-3.20). Composite perinatal morbidity did not differ between groups.
Conclusion:
Outpatient cervical ripening with vaginal isosorbide mononitrate for prolonged pregnancy in nulliparous women does not reduce cesarean delivery rate.
Clinical Trial Registration:
ClinicalTrials.gov, www.clinicaltrials.gov, NCT00930618.
