title: Nifedipine versus atosiban for threatened preterm birth (APOSTEL III): a multicentre, randomised controlled trial.
abstract: BACKGROUND
  In women with threatened preterm birth, delay of delivery by 48 h allows antenatal corticosteroids to improve neonatal outcomes. For this reason, tocolytics are often administered for 48 h; however, there is no consensus about which drug results in the best maternal and neonatal outcomes. In the APOSTEL III trial we aimed to compare the effectiveness and safety of the calcium-channel blocker nifedipine and the oxytocin inhibitor atosiban in women with threatened preterm birth.
  
  
  METHODS
  We did this multicentre, randomised controlled trial in ten tertiary and nine teaching hospitals in the Netherlands and Belgium. Women with threatened preterm birth (gestational age 25-34 weeks) were randomly assigned (1:1) to either oral nifedipine or intravenous atosiban for 48 h. An independent data manager used a web-based computerised programme to randomly assign women in permuted block sizes of four, with groups stratified by centre. Clinicians, outcome assessors, and women were not masked to treatment group. The primary outcome was a composite of adverse perinatal outcomes, which included perinatal mortality, bronchopulmonary dysplasia, sepsis, intraventricular haemorrhage, periventricular leukomalacia, and necrotising enterocolitis. Analysis was done in all women and babies with follow-up data. The study is registered at the Dutch Clinical Trial Registry, number NTR2947.
  
  
  RESULTS
  Between July 6, 2011, and July 7, 2014, we randomly assigned 254 women to nifedipine and 256 to atosiban. Primary outcome data were available for 248 women and 297 babies in the nifedipine group and 255 women and 294 babies in the atosiban group. The primary outcome occurred in 42 babies (14%) in the nifedipine group and in 45 (15%) in the atosiban group (relative risk [RR] 0·91, 95% CI 0·61-1·37). 16 (5%) babies died in the nifedipine group and seven (2%) died in the atosiban group (RR 2·20, 95% CI 0·91-5·33); all deaths were deemed unlikely to be related to the study drug. Maternal adverse events did not differ between groups.
  
  
  CONCLUSIONS
  In women with threatened preterm birth, 48 h of tocolysis with nifedipine or atosiban results in similar perinatal outcomes. Future clinical research should focus on large placebo-controlled trials, powered for perinatal outcomes.
  
  
  BACKGROUND
  ZonMw (the Netherlands Organisation for Health Research and Development).
authors.affiliation: Department of Obstetrics, Wilhelmina Hospital Birth Centre, Division Woman and Baby, University Medical Centre Utrecht, Utrecht, Netherlands.
authors.forename: Elvira O G
authors.initials: EOG
authors.lastname: van Vliet
authors.affiliation: Department of Obstetrics, Wilhelmina Hospital Birth Centre, Division Woman and Baby, University Medical Centre Utrecht, Utrecht, Netherlands.
authors.forename: Tobias A J
authors.initials: TAJ
authors.lastname: Nijman
authors.affiliation: Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, Netherlands; Stanford Prevention Research Center, Stanford University, Stanford, CA, USA.
authors.forename: Ewoud
authors.initials: E
authors.lastname: Schuit
authors.affiliation: Department of Obstetrics, Wilhelmina Hospital Birth Centre, Division Woman and Baby, University Medical Centre Utrecht, Utrecht, Netherlands.
authors.forename: Karst Y
authors.initials: KY
authors.lastname: Heida
authors.affiliation: Clinical Research Unit, Academic Medical Centre, Amsterdam, Netherlands.
authors.forename: Brent C
authors.initials: BC
authors.lastname: Opmeer
authors.affiliation: Department of Obstetrics and Gynecology, Academic Medical Centre, Amsterdam, Netherlands.
authors.forename: Marjolein
authors.initials: M
authors.lastname: Kok
authors.affiliation: Department of Obstetrics and Gynecology, Ziekenhuis Oost-Limburg, Genk, Belgium; Department of Physiology, Hasselt University, Diepenbeek, Belgium.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Gyselaers
authors.affiliation: Department of Obstetrics and Gynaecology, Maxima Medical Centre, Veldhoven, Netherlands.
authors.forename: Martina M
authors.initials: MM
authors.lastname: Porath
authors.affiliation: Department of Obstetrics and Gynaecology, University Medical Centre Nijmegen, Nijmegen, Netherlands.
authors.forename: Mallory
authors.initials: M
authors.lastname: Woiski
authors.affiliation: Department of Obstetrics and Gynaecology, Vrije University Medical Centre, Amsterdam, Netherlands.
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Bax
authors.affiliation: Department of Obstetrics, Wilhelmina Hospital Birth Centre, Division Woman and Baby, University Medical Centre Utrecht, Utrecht, Netherlands; Department of Obstetrics, Leiden University Medical Centre, Leiden, Netherlands.
authors.forename: Kitty W M
authors.initials: KWM
authors.lastname: Bloemenkamp
authors.affiliation: Department of Obstetrics and Gynecology, Maastricht University Medical Centre, Maastricht, Netherlands.
authors.forename: Hubertina C J
authors.initials: HCJ
authors.lastname: Scheepers
authors.affiliation: Department of Gynecology and Obstetrics, Antwerp University Hospital, Antwerp, Belgium.
authors.forename: Yves
authors.initials: Y
authors.lastname: Jacquemyn
authors.affiliation: Department of Obstetrics and Gynaecology, St Antonius Hospital, Nieuwegein, Netherlands.
authors.forename: Erik van
authors.initials: EV
authors.lastname: Beek
authors.affiliation: Department of Obstetrics and Gynecology, Erasmus University Medical Centre, Rotterdam, Netherlands.
authors.forename: Johannes J
authors.initials: JJ
authors.lastname: Duvekot
authors.affiliation: Department of Obstetrics, University Medical Centre, University of Groningen, Groningen, Netherlands.
authors.forename: Maureen T M
authors.initials: MTM
authors.lastname: Franssen
authors.affiliation: Department of Obstetrics and Gynecology, Amphia Hospital, Breda, Netherlands.
authors.forename: Dimitri N
authors.initials: DN
authors.lastname: Papatsonis
authors.affiliation: Department of Neonatology, Academic Medical Centre, Amsterdam, Netherlands.
authors.forename: Joke H
authors.initials: JH
authors.lastname: Kok
authors.affiliation: Department of Obstetrics and Gynecology, Academic Medical Centre, Amsterdam, Netherlands.
authors.forename: Joris A M
authors.initials: JAM
authors.lastname: van der Post
authors.affiliation: Department of Obstetrics, Wilhelmina Hospital Birth Centre, Division Woman and Baby, University Medical Centre Utrecht, Utrecht, Netherlands.
authors.forename: Arie
authors.initials: A
authors.lastname: Franx
authors.affiliation: The Robinson Research Institute, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA, Australia; South Australian Health and Medical Research Institute, Adelaide, SA, Australia.
authors.forename: Ben W
authors.initials: BW
authors.lastname: Mol
authors.affiliation: Department of Obstetrics, Wilhelmina Hospital Birth Centre, Division Woman and Baby, University Medical Centre Utrecht, Utrecht, Netherlands; Department of Obstetrics and Gynecology, Academic Medical Centre, Amsterdam, Netherlands. Electronic address: m.a.oudijk@amc.uva.nl.
authors.forename: Martijn A
authors.initials: MA
authors.lastname: Oudijk
mesh_terms: D061605:Administration, Intravenous; D060433:Administration, Ophthalmic; D000328:Adult; D001530:Belgium; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D009426:Netherlands; D009543:Nifedipine / Q000008:administration & dosage*; D054238:Perinatal Mortality; D011247:Pregnancy; D011256:Pregnancy Outcome; D047928:Premature Birth / Q000517:prevention & control*; D015149:Tocolytic Agents / Q000008:administration & dosage*; D016896:Treatment Outcome; D014668:Vasotocin / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D002121:Calcium Channel Blockers; D015149:Tocolytic Agents; C047046:atosiban; D009543:Nifedipine; D014668:Vasotocin