Randomized Controlled Trial of Pravastatin Sodium for Prolonging Pregnancy in Severe Early-Onset Placental Insufficiency: Focus on Preeclampsia and Intrauterine Growth Restriction

The primary objective of the STATIN-PRE trial is to evaluate the efficacy of daily oral administration of **pravastatin** at a dose of 40 mg in pregnant individuals diagnosed with **preeclampsia** and/or **intrauterine growth restriction** (IUGR) between 24.0 and 29.6 weeks of gestation. The aim is to determine whether this intervention can prolong the duration of pregnancy compared to conventional management strategies. This is clinically relevant as extending the gestational period in such high-risk pregnancies could potentially improve neonatal outcomes and reduce complications associated with preterm birth.

The clinical trial involves a study population of **pregnant individuals** diagnosed with either **preeclampsia** or **intrauterine growth restriction**. Participants are exclusively female, as the conditions under investigation pertain to pregnancy. The age range of the participants falls within categories 3 and 4, which typically correspond to adult age groups. The trial specifically targets a vulnerable population, given the medical conditions and the gestational period of 24.0 to 29.6 weeks. The sponsor has not provided the total number of participants. Selection criteria include having a singleton fetus and being within the specified gestational age at inclusion. Participants must have a diagnosis of early-onset severe preeclampsia or intrauterine growth restriction, as defined by specific clinical parameters, and must be candidates for expectant management without immediate delivery indications. All participants are required to provide informed consent. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed as a **randomized, controlled** study to evaluate the efficacy of daily oral administration of **pravastatin sodium** in pregnant individuals diagnosed with **preeclampsia** and/or **intrauterine growth restriction** between 24.0 and 29.6 weeks of gestation. The primary objective is to assess whether pravastatin can prolong the duration of pregnancy compared to conventional management. The trial will involve two groups: one receiving Pravastatina Kern Pharma 40 mg tablets and the other receiving a placebo. The study is expected to commence recruitment on April 1, 2025, and conclude by December 31, 2027.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as gestational age and diagnosis of early-onset severe preeclampsia or intrauterine growth restriction. Following the screening, participants will be randomized to receive either the active treatment or placebo. Regular follow-up visits will be scheduled to monitor the health of the participants and the progression of the pregnancy. The primary endpoint is the number of days of pregnancy prolongation from inclusion to delivery. The end-of-study visit will occur after delivery to collect final data and ensure participant safety.

The expected duration of participant involvement is up to 10 weeks, depending on the gestational age at inclusion and the timing of delivery. Conditions that may lead to early termination from the study include the need for immediate delivery based on clinical assessments or any adverse events that compromise participant safety. The trial is conducted under a double-blind design, ensuring that neither the participants nor the investigators know which treatment is being administered, thereby minimizing bias and enhancing the reliability of the results.

The clinical trial involves the administration of **Pravastatin Sodium** as the experimental medication. The product used is "Pravastatina Kern Pharma 40 mg comprimidos EFG," which is formulated as a **tablet**. Each tablet contains 40 mg of the active substance, **Pravastatin Sodium**, and is administered orally. The dosing schedule involves a daily administration of one tablet, with a maximum treatment period of 10 days. The medication is manufactured by KERN PHARMA, S.L., and is identified by the European Medicinal Product number PRD375525. The trial aims to assess the efficacy of this treatment in prolonging pregnancy duration in individuals with severe early-onset placental insufficiency.

The study also includes a **placebo** group for comparison. The placebo used is "Placebo Pravastatina," which is designed to mimic the experimental medication in appearance and administration route but contains no active pharmaceutical ingredient. The placebo is administered orally in the same manner as the experimental medication, ensuring blinding of participants and investigators. The placebo serves as a control to evaluate the true efficacy of Pravastatin Sodium in the study population.

The efficacy of the clinical trial titled "Statin Intervention for Severe Early-Onset Placental Insufficiency: A Randomized Controlled Trial Assessing daily Administration as a Treatment Strategy (STATIN-PRE trial)" will be assessed primarily by measuring the **days of prolongation of pregnancy** between inclusion and delivery. This primary endpoint is continuous and will be quantified in days. The trial aims to evaluate whether the daily oral administration of 40 mg of pravastatin in pregnant individuals with preeclampsia (PE) and/or intrauterine growth restriction (IUGR) between 24.0 and 29.6 weeks of gestation can extend the duration of pregnancy compared to conventional management. The assessment will involve a comparison of the duration of pregnancy from the time of inclusion in the trial until delivery. The trial is designed as a Phase III clinical trial, and the estimated recruitment start date is April 1, 2025, with an estimated end date of December 31, 2027.