Nifedipine versus Atosiban in the treatment of threatened preterm labour: APOSTEL III.

Rationale:

Preterm labour is one of the most important obstetric problems throughout the Western world and occurs in approximately 10% of all deliveries. Preterm birth is the leading cause of perinatal mortality (70 %) and accounts for 40 % of severe neurological morbidity. Tocolysis for a period of two days is crucial in the treatment of threatened preterm labour, in order to allow for corticosteroids to exert their optimal effect on fetal lung development. The optimal tocolytic drug however, is subject to controversy. We hypothesize that Nifedipine as compared to Atosiban will result in an improved neonatal outcome.



Objective:

To compare the effectiveness of the tocolytic agents Nifedipine (a calcium channel blocking agent) versus Atosiban (an oxytocin receptor antagonist) in the improvement of neonatal outcome in women with threatened preterm labour (25-34 weeks gestation).



Study design:

Multicenter randomized controlled trial.



Study population:

500 pregnant women with threatened preterm labour between 25 and 34 weeks gestational age.



Intervention:

Nifedipine (dosage: 4 dd 20 mg orally for 48 hours) versus Atosiban (dosage: bolus injection of 6,75 mg i.v. in 1 minute, followed by 18 mg/hour for 3 hours followed by a maintenance dosage of 6 mg/hour for 45 hours) for 48 hours.



Main study parameters/endpoints:

The primary outcome measure will be a composite poor neonatal outcome, including broncho pulmonary dysplasia (BPD), periventricular leucomalacia (PVL) > grade 1, intracerebral haemorrhage > grade 2, necrotising enterocolitis (NEC) > stage 1, proven sepsis and in-hospital death.

Secondary outcomes will be time to delivery, gestational age at delivery, number of days on ventilation support, in NICU and total days of the baby alive outside the hospital counted from a gestational age of 37 weeks and maternal side effects.



Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

As we compare two strategies that are already applied in current practice, no additional risks or burden are expected from the study.

The aim of the study is to compare the effectiveness of tocolysis with Nifedipine or Atosiban in pregnant women with threatened preterm labour with a gestational age between 25 – 34 weeks. We will look at neonatal mortality and morbidity, duration of pregnancy and to maternal side effects.

The outcomes will be registered at time of discharge home or at 36 weeks of corrected GA in case of BPD.

1. In the Nifedipine group, the initial dose will be 20 mg orally in the first hour, followed by 20 mg per 6 hours for the next 47 hours;

2. In the Atosiban group, a Bolus injection of 6,75 mg i.v. in 1 minute, followed by a 18 mg/hour for 3 hours followed by a maintenance dosage of 6 mg/hour for 45 hours.