title: Effectiveness of a cervical pessary for women who did not deliver 48 h after threatened preterm labor (Assessment of perinatal outcome after specific treatment in early labor: Apostel VI trial).
abstract: Preterm birth is a major cause of neonatal mortality and morbidity. As preventive strategies are largely ineffective, threatened preterm labor is a frequent problem that affects approximately 10 % of pregnancies. In recent years, risk assessment in these women has incorporated cervical length measurement and fetal fibronectin testing, and this has improved the capacity to identify women at increased risk for delivery within 14 days. Despite these improvements, risk for preterm birth continues to be increased in women who did not deliver after an episode of threatened preterm labor, as indicated by a preterm birth rate between 30 to 60 % in this group of women. Currently no effective treatment is available. Studies on maintenance tocolysis and progesterone have shown ambiguous results. The pessary has not been evaluated in women with threatened preterm labor, however studies in asymptomatic women with a short cervix show reduced rates of preterm birth rates as well as perinatal complications. The APOSTEL VI trial aims to assess the effectiveness of a cervical pessary in women who did not deliver within 48 h after an episode of threatened preterm labor.
  
  
  
  This is a nationwide multicenter open-label randomized clinical trial. Women with a singleton or twin gestation with intact membranes, who were admitted for threatened preterm labor, at a gestational age between 24 and 34 weeks, a cervical length between 15 and 30 mm and a positive fibronectin test or a cervical length below 15 mm, who did not deliver after 48 h will be eligible for inclusion. Women will be allocated to a pessary or no intervention (usual care). Primary outcome is preterm delivery < 37 weeks. Secondary outcomes are amongst others a composite of perinatal morbidity and mortality. Sample size is based on an expected 50 % reduction of preterm birth before 37 weeks (two-sided test, α 0.05 and β 0.2). Two hundred women with a singleton pregnancy need to be randomized. Analysis will be done by intention to treat.
  
  
  
  The APOSTEL VI trial will provide evidence whether a pessary is effective in preventing preterm birth in women who did not deliver 48 h after admission for threatened preterm labor and who remain at high risk for preterm birth.
  
  
  
  Trial is registered at the Dutch Trial Register: http://www.trialregister.nl , NTR4210, date of registration: October 16th 2013.
authors.affiliation: Department of Obstetrics and Gynaecology, Academic Medical Center, Amsterdam, The Netherlands. f.j.hermans@amc.uva.nl.
authors.forename: Frederik J R
authors.initials: FJ
authors.lastname: Hermans
authors.affiliation: Department of Obstetrics and Gynaecology, Academic Medical Center, Amsterdam, The Netherlands.|Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands.|Stanford Prevention Research Center, Stanford University, Stanford, CA, USA.
authors.forename: Ewoud
authors.initials: E
authors.lastname: Schuit
authors.affiliation: Clinical Research Unit, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Brent C
authors.initials: BC
authors.lastname: Opmeer
authors.affiliation: Department of Obstetrics and Gynaecology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Martijn A
authors.initials: MA
authors.lastname: Oudijk
authors.affiliation: Department of Obstetrics and Gynaecology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Mireille
authors.initials: M
authors.lastname: Bekker
authors.affiliation: Department of Obstetrics and Gynaecology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Mallory
authors.initials: M
authors.lastname: Woiski
authors.affiliation: Department of Obstetrics and Gynaecology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Bax
authors.affiliation: Department of Obstetrics and Gynaecology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Marieke
authors.initials: M
authors.lastname: Sueters
authors.affiliation: Department of Obstetrics and Gynaecology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Hubertina C J
authors.initials: HC
authors.lastname: Scheepers
authors.affiliation: Department of Obstetrics, University Medical Center, University of Groningen, Groningen, The Netherlands.
authors.forename: Maureen T M
authors.initials: MT
authors.lastname: Franssen
authors.affiliation: Department of Obstetrics and Gynaecology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Eva
authors.initials: E
authors.lastname: Pajkrt
authors.affiliation: The Robinson Research Institute, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, Australia.
authors.forename: Ben Willem J
authors.initials: BW
authors.lastname: Mol
authors.affiliation: Department of Obstetrics and Gynaecology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Marjolein
authors.initials: M
authors.lastname: Kok
mesh_terms: D054791:Cervical Length Measurement; D002584:Cervix Uteri / Q000033:anatomy & histology* / Q000000981:diagnostic imaging; D005260:Female; D005353:Fibronectins / Q000097:blood; D006801:Humans; D007752:Obstetric Labor, Premature; D009929:Organ Size; D010570:Pessaries; D011247:Pregnancy; D047928:Premature Birth / Q000517:prevention & control*; D012107:Research Design; D013997:Time Factors
chemical_list: D005353:Fibronectins
keywords: Cervical length; Fetal fibronectin; Pessary; Threatened preterm birth; Treatment