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


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


BACKGROUND
ClinicalTrials.gov NCT00620724.
Department of Obstetrics and Gynecology, Rouen University Hospital, Rouen, France.
Eric
E
Verspyck
Department of Obstetrics and Gynecology, Caen University Hospital, Caen, France.
Claire
C
de Vienne
Department of Obstetrics and Gynecology, Amiens University Hospital, Amiens, France.
Charles
C
Muszynski
Department of Biostatistics, Rouen University Hospital, Rouen, France.
Michael
M
Bubenheim
Department of Obstetrics and Gynecology, Belvedere Hospital, Mont-Saint-Aignan, France.
Isabella
I
Chanavaz-Lacheray
Department of Obstetrics and Gynecology, Caen University Hospital, Caen, France.
Michel
M
Dreyfus
Department of Obstetrics and Gynecology, Lille University, EA 4489-Environnement Périnatal et Santé, Lille, France.
Philippe
P
Deruelle
Inserm U657, University of Rouen and Biostatistics, Rouen, France.
Jacques
J
Benichou
D000328:Adult; D004311:Double-Blind Method; D005260:Female; D005865:Gestational Age; D006801:Humans; D009543:Nifedipine / Q000008:administration & dosage / Q000627:therapeutic use*; D010923:Placenta Previa / Q000188:drug therapy*; D011247:Pregnancy; D011256:Pregnancy Outcome; D015149:Tocolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*
D015149:Tocolytic Agents; D009543:Nifedipine