Single Versus Combination Therapy in Acute Tocolysis
Condition: Preterm Labour
MeSH terms: Premature Birth; Obstetric Labor, Premature
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to compare the tocolytic efficacy, effectiveness and safety of
      Atosiban in comparison with the combination of Atosiban and Nifedipine together.
    

Detailed description: 
      Preterm birth, defined as birth at less than 37+0 weeks of gestation, is the most important
      determinant of adverse infant outcomes. It accounts for 5 to 11% of births in the world, but
      represents the single largest cause of mortality and morbidity for newborns and a major cause
      of morbidity for pregnant women. These babies are at increased risk of cerebral palsies,
      chronic pulmonary insufficiency and other handicaps resulting in suboptimal performance in
      school and decreased abstractive thinking compared with infants born at term. The economic
      burden on society in catering for these preterm babies is high. A multi-level modeling of
      hospital service utilization and cost profile of preterm birth done in 2005 in the United
      Kingdom, has outlined the huge economic consequences of preterm birth in the first 10 years
      of life. Furthermore, recent data from Denmark have shown an overall increase in the
      proportion of preterm deliveries by 22% from 1995 to 2004(from 5.2% to 6.3%). Neonatal
      mortality has declined, mostly due to improved management of very low birth weight babies
      rather than prevention of preterm labor (PTL).

      The most common treatment used in the management of PTL involves pharmacological inhibition
      of preterm uterine contractions. Perinatal death and morbidity resulting from PTL are not
      only strongly related to early gestational age but also to antenatal administration of
      steroids and transfer to a tertiary care centre in utero or after birth.6 Hence, the choice
      of tocolytic agent depends on its ability to delay the delivery by at least 48 hours from the
      time of administration of steroids and preferably longer without maternal or fetal side
      effects. There is considerable variation in the type of tocolytic agent used in different
      parts of the world. Single agent tocolysis using ritodrine (β-agonist), atosiban (oxytocin
      antagonist) or nifedipine (calcium channel blocker) is a common practice. Atosiban has been
      shown to have comparable effectiveness to β-agonists but with improved side-effect profile
      similar to that seen in placebo studies. Meta analysis from Cochrane systematic review failed
      to demonstrate the superiority of atosiban over betamimetics or placebo in terms of tocolytic
      efficacy or infant outcomes, but, the maternal drug reactions that required treatment
      cessation were fewer with atosiban. Nifedipine is the only agent associated with improved
      perinatal outcomes and fewer maternal side-effects than betamimetics. A direct comparison
      between atosiban and nifedipine has shown that both drugs are equally effective in acute
      tocolysis, however maternal side-effects were more pronounced with nifedipine.

      Due to the differences in their pharmacokinetics and pharmacodynamics, one may expect to have
      improved tocolysis when two agents are combined. In vitro studies have demonstrated that
      simultaneous blockade of these different pathways could result in an additive or even
      synergistic effect capable of producing better uterine relaxation than induced by each drug
      alone. Accordingly, the use of multiple agent therapies has been suggested as a way forward
      in tocolytic search. In an observational study, combination therapy without serious side
      effects has been used in the management of PTL at extremely early gestations by Ingemarsson
      et al.3 However, this was not tested in structured human trials.

      The objective of this study was to compare the tocolytic efficacy and safety of the
      combination of atosiban and nifedipine against the single agent, atosiban in the treatment of
      PTL.
    

Intervention name(s): Atosiban; Atosiban and nifedipine
Intervention type(s): Drug; Drug
Intervention description(s): Atosiban was given as a bolus (6.7 mg. IV) over 1 min then an infusion of 18 mg/hr for 3 hrs followed by 6 mg/hr for 48 hrs.; This group were given simultaneously as follows:Atosiban was given as a bolus (6.7 mg. IV) over 1 min then an infusion of 18 mg/hr for 3 hrs followed by 6 mg/hr for 48 hrs.Nifedipine was given in the dose of 10 mg orally every 15 min till uterine quiescence was achieved (<4 contractions/hr). Maximum dose was 40 mg in the first hour then maintenance dose of 10 mg every 4-6 h for 48 hrs was given.
Other intervention name(s): Tractocile; Tractocile and nifedipine
Intervention MeSH terms: Nifedipine; Vasotocin; Atosiban
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Tocolysis; atosiban; nifedipine; combination