TY - JOUR
T1 - Study protocol for a randomised trial for atosiban versus placebo in threatened preterm birth
T2 - The APOSTEL 8 study
AU - Klumper, Job
AU - Breebaart, Wouter
AU - Roos, Carolien
AU - Naaktgeboren, Christiana A.
AU - Van Der Post, Joris
AU - Bosmans, Judith
AU - Van Kaam, Anton
AU - Schuit, Ewoud
AU - Mol, Ben W.
AU - Baalman, Jelle
AU - McAuliffe, Fionnuala
AU - Thornton, Jim
AU - Kok, Marjolein
AU - Oudijk, Martijn A.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - 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).
AB - 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).
KW - atosiban
KW - perinatal outcome
KW - preterm birth
KW - preterm labour
KW - tocolysis
UR - http://www.scopus.com/inward/record.url?scp=85075689555&partnerID=8YFLogxK
U2 - 10.1136/bmjopen-2019-029101
DO - 10.1136/bmjopen-2019-029101
M3 - Article
C2 - 31772083
AN - SCOPUS:85075689555
SN - 2044-6055
VL - 9
JO - BMJ Open
JF - BMJ Open
IS - 11
M1 - e029101
ER -