“Tocolysis in the management of preterm premature rupture of membranes before 34 weeks of gestation:
a double-blinded randomized controlled trial”
Coordinating Investigator : Pr Gilles KAYEM, Hôpital Trousseau, AP-HP, Paris
Scientific Director: : Pr Pierre-Yves ANCEL, INSERM U1153, EPOPé, URC – CIC P1419 et Dre Elsa LORTHE, INSERM U1153, EPOPé
Sponsor : AP-HP
Sources of funding : French Ministry of Health, PHRC N
Scientific justification
PPROM complicates 3% of pregnancies and accounts for one-third of preterm births. It is a leading cause of neonatal mortality and morbidity and increases the risk of maternal infectious morbidity. In cases of early PPROM (22 to 33 completed weeks’ gestation), expectant management is recommended in the absence of labor, chorioamnionitis or fetal distress. Antenatal steroids and antibiotics administration are recommended by international guidelines. However, there is no recommendation regarding tocolysis administration in the setting of PPROM. In theory, reducing uterine contractility should delay delivery and reduce risks of prematurity and neonatal adverse consequences. Likewise, a prolongation of gestation may allow administering a corticosteroids complete course that is associated with a two-fold reduction of morbidity and mortality. However, tocolysis may prolong fetal exposure to inflammation and be associated with higher risk of materno-fetal infection, potentially associated with neonatal death or long-term sequelae, including cerebral palsy.
Main objective:
To assess whether short-term (48 hr) tocolysis reduces perinatal morti-morbidity in cases of PPROM at 22 to 33 completed weeks’ gestation.
Secondary objectives :
Evaluate the impact of post-PPROM tocolysis on pregnancy prolongation, maternal morbidity and minor neonatal morbidity.
Design of the trial :
Double blind randomized controlled trial comparing two parallel groups receiving oral treatment by either Nifedipine or placebo (1:1 ratio).
Population of trial subjects :
Pregnant women with PPROM at 220/7 to 33 6/7 weeks’ gestation.
Investigational medicinal product :
Loading dose : Oral Nifedipine 20 mg prolonged-release at T0 and T0.5 (i.e. 30 min), total=2×20 mg.
Maintenance dose : Oral Nifedipine 20 mg prolonged-release at T3, then 1 pill every 8 hr for 48 hr (i.e. T11, T19, T27, T35 and T43, total=6×20 mg).
Comparator treatment :
Placebo of Nifedipine 20 mg, at T0, T0.5, T3, T11, T19, T27, T35 and T43.
Number of subjects included :
850 women.
Number of sites :
29 centers in France.
Study status :
Inclusion period: 73 months.
Participation period (treatment+follow-up): treatment 48h + follow-up up to 5 years.
Total duration: 133 months.
Etat d’avancement
The study is currently being enrolled until November 6th, 2025.
As of April 15th, 2025, 755 patients have been included.
288 parents have completed and returned the 2-year questionnaire.
Follow-up of all children up to age 5 is currently being organized.