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

Summary

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.

Conditions

• Preeclampsia (PE)
• Hypertension ,Pregnancy

Interventions

DRUG

Dipyridamole 75 MG

Oral dipyridamole 75 mg tablets, administered via a fixed structured dose escalation across the sequential arms described above (75 mg twice daily → three times daily → four times daily). The escalation schedule is identical for all participants; dosing is not individualized and accelerated escalation is not permitted.

Sponsors & Collaborators

• Hadassah Medical Organization

  lead OTHER

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-09-30

Primary Completion

2028-09-30

Completion

2028-09-30

Countries

• Israel

Study Locations