A Phase 1/2 interventional study of Dipyridamole 75 MG in Preeclampsia (PE) and Hypertension ,Pregnancy, sponsored by Hadassah Medical Organization. Not yet recruiting at 1 site in Israel. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-31.
Sponsored by Hadassah Medical Organization · Phase 1/2, Interventional, and Treatment
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.
Study Type: Single-center, open-label, pilot interventional study evaluating an approved medication (dipyridamole) in an off-label indication.
Background and Rationale:
Early-onset preeclampsia (PE), typically presenting before 34 weeks of gestation, is the most severe phenotype of hypertensive pregnancy disease and a leading cause of maternal and perinatal morbidity. Once clinically established, there is no disease-modifying therapy; management relies almost exclusively on close surveillance and timely delivery, frequently resulting in extreme prematurity. Early-onset PE is increasingly recognized as a primarily placental disorder, driven by defective placentation, chronic ischemia-reperfusion injury, progressive trophoblast damage, and maladaptive stress responses, in contrast to late-onset disease, which is more strongly influenced by maternal cardiovascular and metabolic susceptibility.
Prior laboratory research identified ferroptosis, a form of regulated cell death driven by iron-catalyzed peroxidation of membrane phospholipids, as a key mechanism of placental injury in early-onset PE. Human trophoblasts were shown to be uniquely vulnerable to ferroptosis due to their high iron content and intense oxidative metabolism. Using redox phospholipidomics, preeclamptic placentas were shown to accumulate specific hydroperoxy-phosphatidylethanolamine species characteristic of ferroptotic cell death; inducing ferroptosis in placental explants drove sFlt-1 release, and ferroptosis inhibitors reversed both tissue damage and sFlt-1 secretion. Multiple independent groups have since confirmed ferroptosis as a driver of placental injury in preeclampsia.
A high-throughput robotic screen of over 6,500 drugs and compounds, designed to identify pregnancy-safe ferroptosis inhibitors in primary human trophoblast cultures, identified dipyridamole as one of the most potent candidates (EC50 = 0.146 μM), acting independently of its known phosphodiesterase-inhibitory pharmacology. In preeclamptic placental explants, dipyridamole treatment led to a marked and reproducible reduction in sFlt-1 release, a central pathogenic mediator of the maternal syndrome.
From a safety perspective, dipyridamole has an established pregnancy safety record. It is classified as FDA Pregnancy Category B, and a Cochrane meta-analysis of antiplatelet agents in pregnancy confirmed that this drug class is safe and reduces preeclampsia, preterm birth, and small-for-gestational-age births.
Study Rationale Summary:
This study combines a defined molecular target (ferroptosis) with circulating biomarkers (sFlt-1/PlGF ratio) and Doppler parameters that can objectively track placental stress and treatment response, in a population with biomarker-confirmed placental dysfunction expected to deteriorate without intervention. If successful, this pilot would provide preliminary evidence supporting further evaluation of a disease-modifying therapy for established early-onset preeclampsia.
Study Design:
This is a prospective, single-center, open-label pilot study using a sequential, fixed dose-escalation design, evaluating the feasibility and clinical implementation of dipyridamole treatment in women with early-onset preeclampsia, including pharmacokinetic assessment, within standard obstetric care. The study is intentionally designed as a non-randomized pilot; its purpose is not to establish definitive clinical efficacy, but to assess real-world implementability, characterize pharmacokinetics and tolerability during pregnancy, and generate biological and clinical signals to inform the design of a subsequent randomized controlled trial.
Enrollment proceeds through a staged sentinel design: the first participant is enrolled and treated alone, with no further enrollment until she has completed treatment, delivered, and been assessed through the first 24 hours postpartum, and until the independent Safety Monitoring Committee has reviewed the complete safety data and recommended proceeding. Following a favorable review, two additional participants are enrolled, with a second safety gate before enrollment continues toward the planned sample size. This staged approach allows accumulated safety experience to govern each expansion of exposure.
All participants receive dipyridamole in addition to standard clinical management for early-onset preeclampsia, provided in accordance with established international and national guidelines. Study participation does not modify, delay, or replace any component of standard clinical care; decisions regarding antihypertensive therapy, treatment escalation, or delivery timing are made exclusively on clinical grounds by the treating team, independent of study participation. The dose-escalation scheme is fixed and identical for all participants; dosing is not individualized and accelerated escalation is not permitted.
Pharmacokinetic Sampling:
Pharmacokinetic blood samples are drawn, whenever possible, from the participant's existing indwelling intravenous catheter to minimize discomfort. Sparse sampling is performed during the dose-escalation phase, and after reaching the target dose each participant undergoes one intensive pharmacokinetic profiling day, provided maternal and fetal conditions allow a stable sampling window.
Safety Oversight:
Safety oversight is provided by an independent Safety Monitoring Committee comprising five members: an external maternal-fetal medicine specialist, a neonatologist, a hematologist with expertise in coagulation and bleeding risk, a specialist in internal medicine and clinical pharmacology, and an independent epidemiologist/biostatistician. The Committee is independent of the conduct of the study and reviews all serious adverse events, all events meeting a stopping-rule trigger, and cumulative safety data. It governs the staged sentinel enrollment gates and conducts scheduled safety reviews after the first 5 and first 10 participants complete treatment, in addition to any ad hoc reviews triggered by safety events. Final clinical decisions remain with the treating team, with maternal and fetal safety taking priority.
Postpartum follow-up continues to six weeks and includes documentation of adverse events, blood pressure and antihypertensive requirement, readmission, postpartum hemorrhage, infection or surgical complication, and hemoglobin.
916 studies on the registry are indexed under Pre-Eclampsia; 243 are open to participants now.
This study's planned enrollment of 15 is below the median of 110 across 480 interventional studies indexed under Pre-Eclampsia.
Browse Pre-Eclampsia studies →Hadassah Medical Organization is the lead sponsor of 675 studies on the registry; 54 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Initial fixed dose-escalation step. All participants receive oral dipyridamole 75 mg twice daily on Day 1, with clinical monitoring for tolerability prior to escalation to the next dose level.
Drug: Dipyridamole 75 MG
Second fixed dose-escalation step. Participants who tolerate the initial dose escalate to dipyridamole 75 mg three times daily on Day 2. The escalation schedule is fixed and identical for all participants; dosing is not individualized and accelerated escalation is not permitted.
Drug: Dipyridamole 75 MG
Target maintenance dose. Participants escalate to dipyridamole 75 mg four times daily (300 mg/day total) from Day 3 onward, continuing throughout the antepartum period. Study drug is discontinued at least 12 hours before planned delivery, and at least 24 hours before planned delivery at which neuraxial anesthesia is anticipated. Temporary hold or de-escalation to a previously tolerated dose level is permitted based on adverse effects or investigator judgment.
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.
Protocol Feasibility
Composite feasibility endpoint defined as: (1) successful enrollment of ≥10 of 15 planned participants within the recruitment period; (2) completion of the full dose-escalation ramp-up to the target dose of 300 mg/day in ≥70% of enrolled participants; and (3) successful collection of at least the sparse pharmacokinetic sampling set (Day 1 pre-dose + 2 post-dose samples) in ≥70% of participants, within the routine inpatient care setting.
Time frame: From enrollment through delivery (estimated 1-5 weeks per participant)
Peak Plasma Concentration (Cmax) of Dipyridamole
Maximum observed plasma concentration of dipyridamole, estimated from sparse sampling during dose escalation and intensive PK profiling
Time frame: Pre-dose through 6-8 hours post-dose on the intensive PK profiling day (after reaching target dose or highest tolerated dose)
Incidence of Dipyridamole-Related Adverse Events
Number and proportion of participants experiencing adverse events attributed to dipyridamole during the ramp-up and maintenance dosing period (per your protocol's documented AE categories: dizziness, headache, rash, abdominal distress, bleeding). Unit: Number of participants
Time frame: From first drug administration until six weeks postpartum
Change in Serum Soluble fms-Like Tyrosine Kinase-1 (sFlt-1)
Longitudinal change in maternal circulating sFlt-1 concentration following dipyridamole treatment initiation. Unit: pg/mL
Time frame: Daily for the first 7 days, then every 72 hours until delivery
Change in Maternal Blood Pressure
Systolic and diastolic blood pressure trends from treatment initiation to delivery
Time frame: From treatment initiation until delivery (estimated 1-5 weeks)
Pregnancy Latency from Treatment Initiation to Delivery
Number of days from first dose of dipyridamole to delivery, as a measure of the clinical disease trajectory under treatment. unit- days
Time frame: From first dose through delivery (estimated 1-5 weeks)
Uterine Artery Pulsatility Index (UtA-PI)
Serial assessment of uterine artery pulsatility index, measured at baseline and at least twice weekly during treatment, as a measurable indicator of placental vascular resistance and response to treatment. Resistance index (unitless ratio)
Time frame: From enrollment through delivery (estimated 1-5 weeks)
Trough Plasma Concentration (Ctrough) of Dipyridamole
Pre-dose plasma concentration measured at steady state during dose escalation and maintenance dosing
Time frame: From treatment initiation through delivery (estimated 1-5 weeks)
Area Under the Plasma Concentration-Time Curve (AUC) of Dipyridamole
Total systemic exposure to dipyridamole, calculated from the concentration-time profile obtained on the intensive PK profiling day
Time frame: Pre-dose through 6-8 hours post-dose on the intensive PK profiling day
Apparent Oral Clearance (CL/F) of Dipyridamole
Apparent clearance estimated from plasma concentration data using population or non-compartmental PK modeling
Time frame: From treatment initiation through the intensive PK profiling day (estimated 1-5 weeks)
Terminal Elimination Half-Life (t½) of Dipyridamole
Time required for plasma dipyridamole concentration to decrease by half, estimated from the terminal phase of the concentration-time curve
Time frame: Calculated from PK samples collected on the intensive PK profiling day (up to 6-8 hours post-dose)
Need for Initiation or Escalation of Antihypertensive Therapy
Proportion of participants requiring new initiation or dose escalation of antihypertensive medication after treatment start
Time frame: From treatment initiation until delivery (estimated 1-5 weeks)
Overall Antihypertensive Medication Burden
Cumulative antihypertensive drug exposure (e.g., number of agents and/or total dose) during treatment
Time frame: From treatment initiation until delivery (estimated 1-5 weeks)
Change in Serum Placental Growth Factor (PlGF)
Longitudinal change in maternal circulating PlGF concentration following dipyridamole treatment initiation. Unit: pg/mL
Time frame: Daily for the first 7 days, then every 72 hours until delivery
Change in sFlt-1/PlGF Ratio
Longitudinal change in the sFlt-1/PlGF ratio, a composite marker of angiogenic imbalance in placental dysfunction
Time frame: Daily for the first 7 days, then every 72 hours until delivery
Severity of Dipyridamole-Related Adverse Events
Distribution of adverse event severity grades among participants experiencing dipyridamole-related adverse effects Unit: Number of participants (by severity category - e.g., mild/moderate/severe, or CTCAE grade if you're grading formally)
Time frame: From first drug administration until six weeks postpartum
Obstetric Indication for Delivery
Primary clinical reason/indication for delivery, documented for each participant. Number of participants (by indication category)
Time frame: At delivery
Umbilical Artery Pulsatility Index (UA-PI)
Serial assessment of umbilical artery pulsatility index, measured at baseline and at least twice weekly during treatment, as a measurable indicator of placental vascular resistance and fetal-placental circulation. Resistance index (unitless ratio)
Time frame: From enrollment through delivery (estimated 1-5 weeks)
Concentration of Placental Oxidative Stress and Ferroptosis-Related Markers
Assessment of placental tissue obtained at delivery for markers of lipid peroxidation, oxidative stress, and ferroptosis-related pathways, including hydroperoxy-phosphatidylethanolamine species and ferroptosis-associated proteins, compared to historical preeclamptic and normotensive controls.
Time frame: At delivery
Maternal and Fetal Dipyridamole Exposure at Delivery
Maternal and cord blood dipyridamole concentrations measured at delivery to assess transplacental drug transfer and fetal exposure.
Time frame: At delivery
Plan to share: No
Start is estimated for Sep 2026; primary completion for Sep 2028, 24 months later.
How these figures are worked out, and which studies are left out of them.
This study is not yet recruiting, as verified in Jul 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Dipyridamole
Hadassah Medical Organization →