Article Text

Download PDFPDF

Study protocol for a randomised trial for atosiban versus placebo in threatened preterm birth: the APOSTEL 8 study
  1. Job Klumper1,
  2. Wouter Breebaart1,
  3. Carolien Roos1,
  4. Christiana A Naaktgeboren2,
  5. Joris van der Post1,
  6. Judith Bosmans3,
  7. Anton van Kaam4,
  8. Ewoud Schuit2,5,
  9. Ben W Mol6,
  10. Jelle Baalman7,
  11. Fionnuala McAuliffe7,8,
  12. Jim Thornton9,
  13. Marjolein Kok1,
  14. Martijn A Oudijk1
  1. 1 Department of Obstetrics and Gynaecology, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands
  2. 2 University Medical Centre Utrecht, Julius Center for Health Sciences and Primary Care, Utrecht, The Netherlands
  3. 3 Department of Health Sciences, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
  4. 4 Department of Neonatology, Amsterdam UMC, Location AMC and VUmc, Amsterdam, The Netherlands
  5. 5 Standford Prevention Research Center, Stanford University, Stanford, UK
  6. 6 Department of Obstetrics and Gynaecology, School of Medicine, Monash University, Melbourne, Victoria, Australia
  7. 7 Department of Obstetrics and Gynaecology, National Maternity Hospital, Dublin, Ireland
  8. 8 UCD Perinatal Research Centre, University College Dublin, Dublin, Ireland
  9. 9 Department of Obstetrics and Gynaecology, University of Nottingham, Nottingham, UK
  1. Correspondence to Dr Martijn A Oudijk; m.a.oudijk{at}amsterdamumc.nl

Abstract

Introduction Preterm birth complicates >15 million pregnancies annually worldwide. In many countries, women who present with signs of preterm labour are treated with tocolytics for 48 hours. Although this delays birth, it has never been shown to improve neonatal outcome. In 2015, the WHO stated that the use of tocolytics should be reconsidered and that large placebo-controlled studies to evaluate the effectiveness of tocolytics are urgently needed.

Methods and analysis We designed an international, multicentre, randomised, double-blinded, placebo-controlled clinical trial. Women with threatened preterm birth (gestational age 30–34 weeks), defined as uterine contractions with (1) a cervical length of < 15 mm or (2) a cervical length of 15–30 mm and a positive fibronectin test or (3) in centres where cervical length measurement is not part of the local protocol: a positive fibronectin test or insulin-like growth factor binding protein-1 (Actim-Partus test) or (4) ruptured membranes, will be randomly allocated to treatment with atosiban or placebo for 48 hours. The primary outcome is a composite of perinatal mortality and severe neonatal morbidity. Analysis will be by intention to treat. A sample size of 1514 participants (757 per group) will detect a reduction in adverse neonatal outcome from 10% to 6% (alpha 0.05, beta 0.2). A cost-effectiveness analysis will be performed from a societal perspective.

Ethics and dissemination This study has been approved by the Research Ethics Committee (REC) of the Amsterdam University Medical Centres, location AMC, as well as the REC’s in Dublin and the UK. The results will be presented at conferences and published in a peer-reviewed journal. Participants will be informed about the results.

Trial registration number Nederlands Trial Register (Trial NL6469).

  • preterm birth
  • preterm labour
  • tocolysis
  • atosiban
  • perinatal outcome

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

View Full Text

Statistics from Altmetric.com

Footnotes

  • Contributors CAN, JvdP, JB, AvK, ES, BWM, JeB, FM, JT, MK and MAO were involved in conception and design of the study. JK and WB drafted the manuscript. CR, CAN, JvdP, JB, AvK, ES, BWM, JeB, FM, JT, MAO and MK reviewed and edited the manuscript. All authors mentioned in the manuscript are member of the APOSTEL study group or collaborators. They participated in the design of the study during several meetings and are local investigators in the participating centres. All authors edited the manuscript and read and approved the final manuscript

  • Funding This study is funded by ZonMw (The Netherlands organisation for health research and development), grant number 848041004 and the United Kingdom National Institute for Health Research, Clinical Research Network.

  • Competing interests JT received a number of lectures and medical advisory fees from Ferring pharmaceuticals between 2000 and 2016.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.