title: Outpatient cervical ripening by nitric oxide donors for prolonged pregnancy: a randomized controlled trial.
abstract: 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.
  
  
  CONCLUSIONS
  Outpatient cervical ripening with vaginal isosorbide mononitrate for prolonged pregnancy in nulliparous women does not reduce cesarean delivery rate.
  
  
  BACKGROUND
  ClinicalTrials.gov, www.clinicaltrials.gov, NCT00930618.
authors.affiliation: Assistance 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.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmitz
authors.forename: Florent
authors.initials: F
authors.lastname: Fuchs
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Closset
authors.forename: Patrick
authors.initials: P
authors.lastname: Rozenberg
authors.forename: Norbert
authors.initials: N
authors.lastname: Winer
authors.forename: Franck
authors.initials: F
authors.lastname: Perrotin
authors.forename: Eric
authors.initials: E
authors.lastname: Verspyck
authors.forename: Elie
authors.initials: E
authors.lastname: Azria
authors.forename: Bruno
authors.initials: B
authors.lastname: Carbonne
authors.forename: Jacques
authors.initials: J
authors.lastname: Lepercq
authors.forename: Françoise
authors.initials: F
authors.lastname: Maillard
authors.forename: François
authors.initials: F
authors.lastname: Goffinet
mesh_terms: D000328:Adult; D020070:Cervical Ripening / Q000187:drug effects*; D002585:Cesarean Section / Q000706:statistics & numerical data*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D020030:Nitric Oxide Donors / Q000494:pharmacology* / Q000627:therapeutic use; D011247:Pregnancy; D011273:Pregnancy, Prolonged / Q000188:drug therapy*
chemical_list: D020030:Nitric Oxide Donors; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate