Ritodrine in oral maintenance of tocolysis after active preterm labor: randomized controlled trial

Aim

To assess the efficacy of oral ritodrine in the form of sustained-release capsules for maintenance of uterine quiescence after successful treatment of threatened preterm labor.

Methods

We randomized 120 women with singleton pregnancy who were successfully treated for threatened preterm labor before 34 completed weeks to receive either maintenance tocolysis with two 40 mg ritodrine sustained release capsules three times a day (study group, n = 62) or no treatment (control group, n = 58) for three days. The primary outcome measure was the recurrent episode of threatened preterm labor within 72 hours, which was defined as regular palpable uterine contractions and change in cervical effacement or cervical dilatation on clinical examination. Secondary outcome measures included the incidence of preterm birth, neonatal adverse outcomes, and maternal side effects.

Results

There was no difference in the frequency of recurrent episodes of threatened preterm labor requiring another course of intravenous treatment between the study (8/62) and control (6/58) group of women (P = 0.879). No differences were found between the study and control groups in any of the predefined secondary outcome measures, ie, delivery before 37 weeks (13/62 vs 7/58, respectively; P = 0.288), delivery before 34 weeks (3/62 vs 1/58, respectively; P = 0.682) and birth weight (3037 ± 573 g vs 3223 ± 423 g, respectively, P = 0.862). There were more reported maternal side effects in the study group than in control group (47/62 vs 23/58, respectively; P<0.001).

Conclusions

Additional maintenance ritodrine therapy was unnecessary in women with singleton pregnancy who had an episode of threatened preterm labor successfully treated with intravenous tocolytic therapy.

Clinical Trial Registration

ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT00290173","term_id":"NCT00290173"}}NCT00290173A substantial proportion of women experiencing an episode of threatened preterm labor do not progress to delivery if actively treated with intravenous (IV) tocolytic therapy (1). After cessation of IV therapy, many of them continue taking oral tocolytic drugs. However, despite a relatively common use of oral maintenance therapy, there is weak evidence from controlled studies about its effectiveness in these women irrespective of the sort of medication used (1-3). Evidence supporting such approach mostly shows lower incidence of relapses and longer relapse intervals, but no reduction in the frequency of preterm delivery or significant improvement in perinatal mortality and morbidity (1,4-6). Ritodrine is still one of the commonly used drugs in tocolytic therapy (1,5-8). As the bioavailability of ritodrine and its short half life were blamed for its relative inefficacy, the attempt was made to improve them by use of sustained-release preparations (9,10). Except fewer metabolic and cardiovascular side effects, no other important benefits were found. However, ritodrine may have side effects that can be serious not only for the mother, but also for the fetus because it crosses the placenta (5,7,11-13).We performed a prospective randomized controlled trial to determine the effect of oral ritodrine in the form of sustained-release preparation for maintaining uterine quiescence after successful treatment of active preterm labor with ritodrine IV preparations.