Aspirin with or without low‑molecular‑weight heparin to prevent preeclampsia in high‑risk pregnancy

Combined Administration of Low Molecular Weight Heparin and Aspirin Versus Aspirin Alone in Gravidas at High Risk for Preeclampsia: A Randomized Controlled Trial

This trial tests whether adding low‑molecular‑weight heparin (tinzaparin) to low‑dose aspirin reduces the chance of preeclampsia in pregnant people identified as high risk in the first trimester.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: Alexandra Hospital, Athens, Greece (Academic / other)
• Locations: 1 site (Athens, Attica)
• Trial ID: NCT07361679 on ClinicalTrials.gov

What this trial studies

This is a prospective, randomized, single‑center, open‑label trial at Alexandra Hospital in Athens that will enroll 100 singleton pregnancies identified as high risk for preeclampsia (>1:150 by FMF first‑trimester screening). Participants are randomized 1:1 to receive 160 mg daily aspirin alone or 160 mg aspirin plus weight‑adjusted therapeutic tinzaparin from before 16 weeks until 36 weeks gestation. The primary outcome is incidence of preeclampsia, with secondary outcomes including early preeclampsia, gestational hypertension, HELLP, preterm birth, fetal growth restriction, placental abruption, and neonatal outcomes. Blood samples at 20–24, 32–34, and 36 weeks will measure PlGF, sFlt‑1, inflammatory markers, and related biomarker ratios, and regular telephone follow‑up will monitor adherence and adverse events.

Who should consider this trial

Good fit: Pregnant people aged 18 or older with a singleton pregnancy under 16 weeks and a calculated FMF first‑trimester preeclampsia risk >1:150 who can provide informed consent and complete follow‑up are ideal candidates.

Not a fit: Those with multiple pregnancy, contraindications to aspirin or heparin (including bleeding disorders or prior heparin‑induced thrombocytopenia), severe renal failure, or otherwise low preeclampsia risk are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, adding LMWH to aspirin could significantly lower rates of preeclampsia and its maternal and neonatal complications in high‑risk pregnancies.

How similar studies have performed: Low‑dose aspirin started in the first trimester is proven to reduce preeclampsia risk in high‑risk women, but evidence that adding LMWH provides extra benefit is limited and has been mixed.

Eligibility criteria

Inclusion Criteria:

* Singleton pregnancy
* High risk for preeclampsia (risk \>1:150) based on FMF screening algorithm combining first-trimester ultrasound, biochemical markers, and medical history
* Gestational age \<16 weeks at enrollment
* Maternal age ≥18 years
* Willing and able to provide written informed consent
* Adequate ability for follow-up (direct telephone communication, accessible residence)

Exclusion Criteria:

* Multiple pregnancy
* Current permanent aspirin use for other medical indications
* Serious congenital fetal abnormality detected on ultrasound
* Contraindication to aspirin or low molecular weight heparin including: known hypersensitivity, active peptic ulcer disease, bleeding disorders or coagulopathy, severe thrombocytopenia (platelet count \<100,000/μL), active or recent significant bleeding, history of heparin-induced thrombocytopenia
* Pre-existing severe renal failure (creatinine clearance \<30 mL/min)
* Unable to provide informed consent
* Low probability of adequate follow-up (residence in remote areas without telephone access, accommodation in temporary structures)

Where this trial is running

Athens, Attica

• First Department of Obstetrics and Gynecology, Alexandra Hospital — Athens, Attica, Greece (Recruiting)

Study contacts

• Study coordinator: Dimitrios Baroutis, MD, MSc, PhD(c)

Conditions Preeclampsia Severe; Toxemia Of Pregnancy; Preeclampsia; Pregnancy Complications; Hypertension, Pregnancy-Induced; Gestational Hypertension; preeclampsia; gestational hypertension