Nifedipine Tocolysis in Preterm Premature Rupture of Membranes Before 34 Weeks: A Double-Blind Randomized Controlled Trial

The primary objective of this study is to evaluate whether short-term (48-hour) **tocolysis** reduces perinatal morti-morbidity in cases of preterm premature rupture of membranes (PPROM) at 22 to 33 completed weeks of gestation. This is clinically relevant as it aims to improve outcomes for both the mother and neonate by potentially decreasing the risks associated with early delivery.

Secondary objectives include assessing the impact of 48-hour tocolysis on latency duration, maternal morbidity, and neonatal minor morbidity in cases of PPROM at 22 to 33 weeks' gestation. These objectives are important for understanding the broader implications of tocolysis on maternal and neonatal health beyond immediate perinatal outcomes.

The clinical trial focuses on a **study population** consisting exclusively of female participants, as the condition under investigation is related to **obstetric pathological delivery**. The trial does not provide specific data on the total number of participants, as the sponsor has not disclosed this information. Participants are selected based on the presence of preterm premature rupture of membranes (PPROM) between 22 0/7 and 33 6/7 weeks of gestation, with the requirement that the fetus is alive at the time of randomization. The age range for participants is 18 years and older, and they must be French-speaking and affiliated with social security or an equivalent system. The trial does not involve a vulnerable population, and lifestyle considerations such as diet and physical activity are not specified. The selection criteria ensure that participants have a singleton gestation and have provided informed consent. The trial aims to assess the impact of short-term tocolysis on perinatal morti-morbidity in cases of PPROM.

The clinical trial is designed as a **double-blind**, **randomized**, and **controlled** study to evaluate the efficacy of short-term tocolysis in reducing perinatal morti-morbidity in cases of preterm premature rupture of membranes (PPROM) between 22 and 33 completed weeks of gestation. The trial involves the administration of **nifedipine**, a **prolonged-release tablet**, and a placebo, both administered orally. The study aims to assess the primary endpoint, which is a composite outcome including fetal death, neonatal death up to discharge from the hospital, and/or neonatal severe morbidity. Secondary endpoints include the prolongation of gestation, maternal morbidity, neonatal minor morbidity, and outcomes at two years of corrected age.

The trial is expected to run from July 2019 to April 2027. Participants will be involved in the study for a maximum treatment period of two weeks. The inclusion criteria require participants to have a singleton gestation, be 18 years or older, French-speaking, and affiliated with social security or an equivalent system. Participants must provide informed consent. The study begins with a screening visit to confirm eligibility, followed by randomization. Subsequent visits will monitor the health of the mother and fetus, assess the efficacy of the treatment, and record any adverse events. The end-of-study visit will evaluate the primary and secondary endpoints.

Participants may be withdrawn from the study if they experience significant adverse effects, withdraw consent, or if the investigator deems it necessary for safety reasons. The trial is conducted under strict ethical guidelines, ensuring the safety and well-being of all participants. The study's findings will contribute to understanding the management of PPROM and potentially improve clinical outcomes for affected pregnancies.

The clinical trial involves the administration of **Nifedipine**, an experimental medication, in the form of a **prolonged-release tablet**. The active substance, **nifedipine**, is of chemical origin. The medication is administered orally, with a maximum daily dose of 100 mg and a total maximum dose of 160 mg over the course of the treatment. The treatment period is limited to a maximum of 2 days. The primary objective of the trial is to evaluate the efficacy of short-term tocolysis in reducing perinatal mortality and morbidity in cases of preterm premature rupture of membranes (PPROM) between 22 and 33 completed weeks of gestation.

In addition to the experimental medication, a **placebo** of Nifedipine is used as a comparator treatment in this double-blinded randomized controlled trial. The placebo is designed to mimic the appearance of the Nifedipine tablets but does not contain any active pharmaceutical ingredients. The placebo is administered in the same manner as the experimental medication, ensuring that the study remains blinded and that any observed effects can be attributed to the active treatment. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.

Efficacy in this clinical trial will be assessed through a combination of primary and secondary endpoints. The primary endpoint is a composite outcome that includes **fetal death**, neonatal death up to discharge from the hospital, and/or neonatal severe morbidity. This endpoint will provide a comprehensive measure of the intervention's impact on critical perinatal outcomes.

Secondary endpoints will include the prolongation of gestation, maternal morbidity, neonatal minor morbidity, and outcomes at 2 years of corrected age. These endpoints will offer additional insights into the broader effects of the treatment on both maternal and neonatal health. The assessment of these endpoints will be conducted at various timepoints throughout the trial, ensuring a thorough evaluation of the treatment's efficacy over time.