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Nifedipine versus atosiban for threatened preterm birth (APOSTEL III): a multicentre, randomised controlled trial.
Lancet. 2016 May 21; 387(10033):2117-2124.Lct

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.

FINDINGS

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.

INTERPRETATION

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.

FUNDING

ZonMw (the Netherlands Organisation for Health Research and Development).

Authors+Show Affiliations

Department of Obstetrics, Wilhelmina Hospital Birth Centre, Division Woman and Baby, University Medical Centre Utrecht, Utrecht, Netherlands.Department of Obstetrics, Wilhelmina Hospital Birth Centre, Division Woman and Baby, University Medical Centre Utrecht, Utrecht, Netherlands.Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, Netherlands; Stanford Prevention Research Center, Stanford University, Stanford, CA, USA.Department of Obstetrics, Wilhelmina Hospital Birth Centre, Division Woman and Baby, University Medical Centre Utrecht, Utrecht, Netherlands.Clinical Research Unit, Academic Medical Centre, Amsterdam, Netherlands.Department of Obstetrics and Gynecology, Academic Medical Centre, Amsterdam, Netherlands.Department of Obstetrics and Gynecology, Ziekenhuis Oost-Limburg, Genk, Belgium; Department of Physiology, Hasselt University, Diepenbeek, Belgium.Department of Obstetrics and Gynaecology, Maxima Medical Centre, Veldhoven, Netherlands.Department of Obstetrics and Gynaecology, University Medical Centre Nijmegen, Nijmegen, Netherlands.Department of Obstetrics and Gynaecology, Vrije University Medical Centre, Amsterdam, Netherlands.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.Department of Obstetrics and Gynecology, Maastricht University Medical Centre, Maastricht, Netherlands.Department of Gynecology and Obstetrics, Antwerp University Hospital, Antwerp, Belgium.Department of Obstetrics and Gynaecology, St Antonius Hospital, Nieuwegein, Netherlands.Department of Obstetrics and Gynecology, Erasmus University Medical Centre, Rotterdam, Netherlands.Department of Obstetrics, University Medical Centre, University of Groningen, Groningen, Netherlands.Department of Obstetrics and Gynecology, Amphia Hospital, Breda, Netherlands.Department of Neonatology, Academic Medical Centre, Amsterdam, Netherlands.Department of Obstetrics and Gynecology, Academic Medical Centre, Amsterdam, Netherlands.Department of Obstetrics, Wilhelmina Hospital Birth Centre, Division Woman and Baby, University Medical Centre Utrecht, Utrecht, Netherlands.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.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.

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26944026

Citation

van Vliet, Elvira O G., et al. "Nifedipine Versus Atosiban for Threatened Preterm Birth (APOSTEL III): a Multicentre, Randomised Controlled Trial." Lancet (London, England), vol. 387, no. 10033, 2016, pp. 2117-2124.
van Vliet EOG, Nijman TAJ, Schuit E, et al. Nifedipine versus atosiban for threatened preterm birth (APOSTEL III): a multicentre, randomised controlled trial. Lancet. 2016;387(10033):2117-2124.
van Vliet, E. O. G., Nijman, T. A. J., Schuit, E., Heida, K. Y., Opmeer, B. C., Kok, M., Gyselaers, W., Porath, M. M., Woiski, M., Bax, C. J., Bloemenkamp, K. W. M., Scheepers, H. C. J., Jacquemyn, Y., Beek, E. V., Duvekot, J. J., Franssen, M. T. M., Papatsonis, D. N., Kok, J. H., van der Post, J. A. M., ... Oudijk, M. A. (2016). Nifedipine versus atosiban for threatened preterm birth (APOSTEL III): a multicentre, randomised controlled trial. Lancet (London, England), 387(10033), 2117-2124. https://doi.org/10.1016/S0140-6736(16)00548-1
van Vliet EOG, et al. Nifedipine Versus Atosiban for Threatened Preterm Birth (APOSTEL III): a Multicentre, Randomised Controlled Trial. Lancet. 2016 May 21;387(10033):2117-2124. PubMed PMID: 26944026.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nifedipine versus atosiban for threatened preterm birth (APOSTEL III): a multicentre, randomised controlled trial. AU - van Vliet,Elvira O G, AU - Nijman,Tobias A J, AU - Schuit,Ewoud, AU - Heida,Karst Y, AU - Opmeer,Brent C, AU - Kok,Marjolein, AU - Gyselaers,Wilfried, AU - Porath,Martina M, AU - Woiski,Mallory, AU - Bax,Caroline J, AU - Bloemenkamp,Kitty W M, AU - Scheepers,Hubertina C J, AU - Jacquemyn,Yves, AU - Beek,Erik van, AU - Duvekot,Johannes J, AU - Franssen,Maureen T M, AU - Papatsonis,Dimitri N, AU - Kok,Joke H, AU - van der Post,Joris A M, AU - Franx,Arie, AU - Mol,Ben W, AU - Oudijk,Martijn A, Y1 - 2016/03/02/ PY - 2016/3/6/entrez PY - 2016/3/6/pubmed PY - 2016/7/7/medline SP - 2117 EP - 2124 JF - Lancet (London, England) JO - Lancet VL - 387 IS - 10033 N2 - 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: ZonMw (the Netherlands Organisation for Health Research and Development). SN - 1474-547X UR - https://www.unboundmedicine.com/medline/citation/26944026/Nifedipine_versus_atosiban_for_threatened_preterm_birth__APOSTEL_III_:_a_multicentre_randomised_controlled_trial_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(16)00548-1 DB - PRIME DP - Unbound Medicine ER -