Maintenance nifedipine therapy for preterm symptomatic placenta previa: A randomized, multicenter, double-blind, placebo-controlled trial

PLoS One. 2017 Mar 23;12(3):e0173717. doi: 10.1371/journal.pone.0173717. eCollection 2017.

Abstract

Objective: To assess the impact of maintenance nifedipine therapy on pregnancy duration in women with preterm placenta previa bleeding.

Methods: PPADAL was a randomized, double-blind, placebo-controlled trial conducted between 05/2008 and 05/2012 in five French hospitals. The trial included 109 women, aged ≥ 18 years, with at least one episode of placenta previa bleeding, intact membranes and no other pregnancy complication, at gestational age 24 to 34 weeks and after 48 hours of complete acute tocolysis. Women were randomly allocated to receive either 20 mg of slow-release nifedipine three times daily (n = 54) or placebo (n = 55) until 36 + 6 weeks of gestation. The primary outcome for the trial was length of pregnancy measured in days after enrolment. Main secondary outcomes were rates of recurrent bleeding, cesarean delivery due to hemorrhage, blood transfusion, maternal side effects, gestational age at delivery and adverse perinatal outcomes (perinatal death, chronic lung disease, neonatal sepsis, intraventricular hemorrhage > grade 2, perventricular leukomalacia > grade 1, or necrotizing enterocolitis). Analysis was by intention to treat.

Results: Mean (SD) prolongation of pregnancy was not different between the nifedipine (n = 54) and the placebo (n = 55) group; 42.5 days ± 23.8 versus 44.2 days ± 24.5, p = 0.70. Cesarean due to hemorrhage performed before 37 weeks occurred more frequently in the nifedipine group in comparison with the placebo group (RR, 1.66; 95% confidence interval, 1.05-2.72). Adverse perinatal outcomes were comparable between groups; 3.8% for nifedipine versus 5.5% for placebo (relative risk, 0.52; 95% confidence interval 0.10-2.61). No maternal mortality or perinatal death occurred.

Conclusion: Maintenance oral nifedipine neither prolongs duration of pregnancy nor improves maternal or perinatal outcomes.

Trial registration: ClinicalTrials.gov NCT00620724.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Double-Blind Method
  • Female
  • Gestational Age
  • Humans
  • Nifedipine / administration & dosage
  • Nifedipine / therapeutic use*
  • Placenta Previa / drug therapy*
  • Pregnancy
  • Pregnancy Outcome
  • Tocolytic Agents / administration & dosage
  • Tocolytic Agents / therapeutic use*

Substances

  • Tocolytic Agents
  • Nifedipine

Associated data

  • ClinicalTrials.gov/NCT00620724

Grant support

This study was only funded by the clinical research program for hospitals (PHRC) of the French Health Ministry. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. We also confirm that no authors received a salary from the funders.