Dipyridamole Added to Hospital Care for Early-Onset Preeclampsia in Pregnancy

Trial details

Who runs it

Hadassah Medical Organization

Trial code

NCT07738562

Record updated

31 July 2026

Original description

Early-onset preeclampsia (PE), defined as preeclampsia presenting before 34 weeks of gestation, is a severe placental disorder associated with significant maternal and perinatal morbidity. There is currently no disease-modifying treatment; management relies on close surveillance and delivery, frequently resulting in extreme prematurity.Read full original descriptionShow less

Dipyridamole for Early-Onset Preeclampsia: A Pilot Study of Feasibility, Pharmacokinetics, and Biological Effects

Early-onset preeclampsia (PE), defined as preeclampsia presenting before 34 weeks of gestation, is a severe placental disorder associated with significant maternal and perinatal morbidity. There is currently no disease-modifying treatment; management relies on close surveillance and delivery, frequently resulting in extreme prematurity.

Recent laboratory research identified ferroptosis, a form of iron-dependent regulated cell death driven by lipid peroxidation, as a key mechanism of placental injury in early-onset preeclampsia. A high-throughput drug screen identified dipyridamole, an approved oral antiplatelet and vasodilatory agent, as a potent ferroptosis inhibitor in primary human trophoblast cultures (EC50 = 0.146 µM), acting through mechanisms independent of its known phosphodiesterase-inhibitory pharmacology. In preeclamptic placental explants, dipyridamole markedly reduced release of sFlt-1, a central mediator of the maternal syndrome. Dipyridamole carries an established pregnancy safety record supported by randomized trials and a Cochrane meta-analysis of antiplatelet agents in pregnancy.

This is a prospective, single-center, open-label pilot study using a sequential, fixed dose-escalation design. The study will enroll 15 hospitalized pregnant women with early-onset preeclampsia (gestational age 26+0 to 33+6 weeks) and an elevated sFlt-1/PlGF ratio (≥85), for whom expectant management is clinically appropriate. Enrollment proceeds through a staged sentinel design with safety gates reviewed by an independent Safety Monitoring Committee. Participants receive oral dipyridamole added to standard clinical care, using a fixed dose-escalation protocol (75 mg twice daily on Day 1, escalating over 2-3 days to a target dose of 75 mg four times daily, 300 mg/day total). Standard obstetric care continues unchanged, determined entirely on clinical grounds, independent of study participation.

The primary objective is to evaluate the feasibility and clinical implementability of the dipyridamole treatment protocol within routine inpatient obstetric care. Secondary objectives include characterizing the pharmacokinetics of dipyridamole during pregnancy, assessing tolerability, and evaluating longitudinal circulating angiogenic biomarkers (sFlt-1 and PlGF). Exploratory objectives include assessment of placental markers of oxidative stress and ferroptosis-related pathways in tissue obtained at delivery.

Study drug is administered during the antepartum period only and discontinued before delivery. This pilot study is not designed to establish clinical efficacy, but to provide the pharmacokinetic, tolerability, and biological data required to design a subsequent randomized trial.

Exclusion: Immediate indication for delivery at time of screening, including uncontrolled severe hypertension, eclampsia, HELLP syndrome, or severe fetal compromise; Active maternal bleeding or clinically significant bleeding disorder; Known hypersensitivity or contraindication to dipyridamole; Hemodynamically significant maternal cardiac disease; Baseline thrombocytopenia, platelet count <100,000/µL; Therapeutic-dose anticoagulation (e.g., enoxaparin >1 mg/kg/day); Multiple gestation; Known major fetal anomaly or chromosomal abnormality; Significant maternal comorbidity that, in the investigator's judgment, precludes safe participation; Inability to comply with study procedures.

Age ≥ 18 years; Singleton pregnancy; Established early-onset preeclampsia, with or without severe features, with gestational age from 26+0 to 33+6 weeks at enrollment, confirmed by best obstetric estimate; Hospitalization for maternal and/or fetal surveillance; Expectant management deemed appropriate by the treating clinical team at the time of enrollment; sFlt-1/PlGF ratio ≥85 at screening; Confirmed viable fetus without a known or suspected major structural or chromosomal anomaly; Baseline platelet count ≥100,000/µL; Ability to provide written informed consent.

ClinicalTrials.gov NCT07738562