Nifedipine versus atosiban in the treatment of threatened preterm labour (Assessment of Perinatal Outcome after Specific Tocolysis in Early Labour: APOSTEL III-Trial)

BMC Pregnancy and Childbirth

Martijn A Oudijk⁸  Ben Willem J Mol^1,13  Arie Franx⁸  Joke H Kok^1,11  Bas N Bijvank²  Maureen TM Franssen³  Hans JJ Duvekot^1,17  Erik van Beek^1,15  Yves Jaquemyn^1,14  Hubertina CJ Scheepers⁵  Kitty WM Bloemenkamp⁴  Caroline J Bax⁹  Mallory Woiski⁶  Martina M Porath⁷  Wilfried Gyselaers^1,10  Marjolein Kok¹  Brent C Opmeer^1,12  Karst Y Heida^1,16  Ewoud Schuit^1,16  Elvira OG van Vliet⁸ 

[1] Department of Obstetrics and Gynaecology, Academic Medical Centre, Amsterdam, the Netherlands;Department of Obstetrics and Gynaecology, Isala Clinics, Zwolle, the Netherlands;Department of Obstetrics, University Medical Centre, University of Groningen, Groningen, the Netherlands;Department of Obstetrics and Gynaecology, Leiden University Medical Centre, Leiden, the Netherlands;Department of Obstetrics and Gynaecology, Maastricht University Medical Centre, Maastricht, the Netherlands;Department of Obstetrics and Gynaecology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands;Department of Obstetrics and Gynaecology, Máxima Medical Centre, Veldhoven, the Netherlands;Department of Obstetrics and Gynaecology, University Medical Centre Utrecht, Utrecht, the Netherlands;Department of Obstetrics and Gynaecology, VU Medical Centre, Amsterdam, the Netherlands;Department of Physiology, Hasselt University, Diepenbeek, Belgium;Department of Neonatology, Academic Medical Centre, Amsterdam, the Netherlands;Clinical Research Unit, Academic Medical Centre, Amsterdam, the Netherlands;The Robinson Institute, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, Australia;Department of Gynecology and Obstaetrics, Antwerp University Hospital, Antwerp, Belgium;Department of Obstetrics and Gynaecology, Sint Antonius Hospital, Nieuwegein, the Netherlands;Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, the Netherlands;Department of Obstetrics and Gynaecology, Erasmus Medical Centre, Rotterdam, the Netherlands

关键词: Drug safety;    Outcome;    Atosiban;    Nifedipine;    Tocolytics;    Preterm birth;   

Others  :  1127525
DOI  :  10.1186/1471-2393-14-93

 received in 2014-01-29, accepted in 2014-02-27,  发布年份 2014

【 摘 要 】

Background

Preterm birth is the most common cause of neonatal morbidity and mortality. Postponing delivery for 48 hours with tocolytics to allow for maternal steroid administration and antenatal transportation to a centre with neonatal intensive care unit facilities is the standard treatment for women with threatening preterm delivery in most centres. However, there is controversy as to which tocolytic agent is the drug of first choice. Previous trials have focused on tocolytic efficacy and side effects, and are probably underpowered to detect clinically meaningfull differences in neonatal outcome. Thus, the current evidence is inconclusive to support a balanced recommendation for clinical practice. This multicenter randomised clinical trial aims to compare nifedipine and atosiban in terms of neonatal outcome, duration of pregnancy and maternal side effects.

Methods/Design

The Apostel III trial is a nationwide multicenter randomised controlled study. Women with threatened preterm labour (gestational age 25 – 34 weeks) defined as at least 3 contractions per 30 minutes, and 1) a cervical length of ≤ 10 mm or 2) a cervical length of 11-30 mm and a positive Fibronectin test or 3) ruptured membranes will be randomly allocated to treatment with nifedipine or atosiban. Primary outcome is a composite measure of severe neonatal morbidity and mortality. Secondary outcomes will be time to delivery, gestational age at delivery, days on ventilation support, neonatal intensive care (NICU) admittance, length admission in neonatal intensive care, total days in hospital until 3 months corrected age, convulsions, apnoea, asphyxia, proven meningitis, pneumothorax, maternal side effects and costs. Furthermore, an economic evaluation of the treatment will be performed. Analysis will be by intention to treat principle. The power calculation is based on an expected 10% difference in the prevalence of adverse neonatal outcome. This implies that 500 women have to be randomised (two sided test, β 0.2 at alpha 0.05).

Discussion

This trial will provide evidence on the optimal drug of choice in acute tocolysis in threatening preterm labour.

Trial registration

Clinical trial registration: NTR2947, date of registration: June 20th 2011.

【 授权许可】

   
2014 van Vliet et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Berkowitz GS, Papiernik E: Epidemiology of preterm birth. Epidemiol Rev 1993, 15:414-443.
• [2]Slattery MM, Morrison JJ: Preterm birth. Lancet 2002, 360:1489-1497.
• [3]Zeitlin J, Szamotulska K, Drewniak N, Mohangoo A, Chalmers J, Sakkeus L, Irgens L, Gatt M, Gissler M, Blondel B: Preterm birth. BJOG 2013, 120:1356-1365.
• [4]Ananth A, Cintzileos A: Epidemiology of preterm birth and its clinical subtypes. J Matern Fetal Neonatal Med 2006, 19:773-782.
• [5]Goldenberg RL, Culhane JF, Iams JD, Romero R: Epidemiology and causes of preterm birth. Lancet 2008, 371:75-84.
• [6]Gilbert WM, Nesbitt TS, Danielsen B: The costs of prematurity: quantification by gestational age and birth weight. Obstet Gynecol 2003, 102:488-492.
• [7]Moore T, Hennessy EM, Myles J, Johnson JS, Draper ES, Costeloe KL, Marlow NJ: Neurological and developmental outcome in extremely preterm children born in England in 1995 and 2006: the EPICure studies. BMJ 2012, 345:e7961.
• [8]Roberts D, Dalziel S: Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev 2006, 19(3):CD004454.
• [9]Rautava L, Eskelinen J, Häkkinen U, Lehtonen L: 5-year morbidity among very preterm infants in relation to level of hospital care. JAMA Pediatr 2013, 167(1):40-46.
• [10]Hehiri MP, O’Connor HD, Kent EM, Robson MS, Keane DP, Geary MP, Malone FD: Early and late preterm delivery rates- a comparison of differing tocolytic policies in a single urban population. J Matern Fetal Neonatal Med 2012, 25(11):2234-2236.
• [11]Haas DM, Imperiale TF, Kirkpatrick PR, Klein RW, Zollinger TW, Golichowski AM: Tocolytic therapy: a meta-analysis and decision analysis. Obstet Gynecol 2009, 113(3):585-594.
• [12]Haas DM, Caldwell DM, Kirkpatrick P, McIntosh JJ, Welton NJ: Tocolytic therapy for preterm delivery: systematic review and network meta-analysis. BMJ 2012, 345:e6226.
• [13]Berkman ND, Thorp JM Jr, Lohr KN, Carey TS, Hartmann KE, Gavin NI, Hasselblad V, Idicula AE: Tocolytic treatment for the management of preterm labor: A review of the evidence. Am J Obstet Gynecol 2003, 188(6):1648-1659.
• [14]King JF, Flenady VJ, Papatsonis DN, Dekker GA, Carbonne B: Calcium channel blockers for inhibiting preterm labour. Cochrane Database Syst Rev 2003, 1:CD002255.
• [15]Papatsonis D, Flenady V, Cole S, Liley H: Oxytocin receptor antagonists for inhibiting preterm labour. Cochrane Database Syst Rev 2005, 20(3):CD004452.
• [16]van Veen AJ, Pelinck MJ, van Pampus MG, Erwich JJ: Severe hypotension and fetal death due to tocolysis with nifedipine. BJOG 2005, 112(4):509-510.
• [17]de Heus R, Mol BW, Erwich JJ, van Geijn HP, Gyselaers WJ, Hanssens M, Härmark L, van Holsbeke CD, Duvekot JJ, Schobben FF, Wolf H, Visser GH: Adverse drug reactions to tocolytic treatment for preterm labour: prospective cohort study. BMJ 2009, 338:b744.
• [18]Kashanian M, Akbarian AR, Soltanzadeh M: Atosiban and nifedipin for the treatment of preterm labor. Int J Gynaecol Obstet 2005, 91:10-14.
• [19]Al-Omari WR, Al-Shammaa HB, Al-Tikriti EM, Ahmed KW: Atosiban and nifedipine in acute tocolysis: a comparative study. Eur J Obstet Gynecol Reprod Biol 2006, 128:129-134.
• [20]Salim R, Garmi G, Nachum Z, Zafran N, Baram S, Shalev E: Nifedipine compared with atosiban for treating preterm labor. Obstet Gynecol 2012, 120:1323-1331.
• [21]Bell MJ: Neonatal necrotizing enterocolitis. Ann Surg 1978, 187:1-7.
• [22]Jobe AH, Bancalari E: Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001, 163:1723-1729.
• [23]de Vries LS, Eken P, Dubowitz LM: The spectrum of leukomalacia using cranial ultrasound. Behav Brain Res 1992, 49:1-6.
• [24]Ment LR, Bada HS, Barnes P, Grant PE, Hirtz D, Papile LA, Pinto-Martin J, Rivkin M, Slovis TL: Practice parameter: neuroimaging of the neonate: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology 2002, 58(12):1726-1738.