LDA and LMWH vs LDA Alone in High-risk Patients for Preeclampsia Prevention (preGO)

January 15, 2026 updated by: Georgios Daskalakis, Alexandra Hospital, Athens, Greece

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

Preeclampsia is a major cause of maternal and perinatal morbidity and mortality worldwide. Low-dose aspirin started in the first trimester reduces the risk of preeclampsia in high-risk women. Low molecular weight heparin (LMWH) has shown potential benefits in addition to aspirin for preventing preeclampsia through its anticoagulant, anti-inflammatory, and endothelial protective effects. However, current evidence is limited and conflicting regarding the added value of LMWH to aspirin. This randomized controlled trial aims to evaluate the efficacy of combined aspirin and LMWH, compared to aspirin alone, for reducing the incidence of preeclampsia in high-risk gravidas.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a prospective, randomized, single-center, open-label trial conducted at the First Obstetrics and Gynecology Clinic of Alexandra Hospital, Athens, Greece. One hundred pregnant women at high risk of preeclampsia (risk >1:150) will be randomly allocated 1:1 to receive either 160mg aspirin daily (n=50) or 160mg aspirin plus weight-adjusted therapeutic doses of LMWH (tinzaparin 4,500-8,000 IU daily based on weight) (n=50) initiated before 16 weeks gestation until 36 weeks.

Risk assessment will be performed using the internationally recognized FMF (Fetal Medicine Foundation) model, combining first trimester ultrasound examination, biochemical markers, and individual medical history.

The primary outcome is the incidence of preeclampsia. Secondary outcomes include development of early preeclampsia (<34 weeks), gestational hypertension, HELLP syndrome, spontaneous preterm labor, intrauterine growth restriction, placental abruption, and various neonatal outcomes.

Blood samples will be collected at 20-24, 32-34, and 36 weeks to measure biomarkers including PlGF, sFlt-1, E-Selectin, IL-1β, IL-6, IL-10, TNF-α, sFlt-1/PlGF ratio, and systemic immune-inflammation index (SII). Regular telephone follow-up will be conducted to monitor adherence and adverse events.

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Dimitrios Baroutis, MD, MSc, PhD(c)
  • Phone Number: +306978275745
  • Email: dbaroutis@gmail.com

Study Locations

  • Greece
    • Attica
      • Athens, Attica, Greece, 11528
        • Recruiting
        • First Department of Obstetrics and Gynecology, Alexandra Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Georgios Daskalakis, MD, PhD
        • Principal Investigator:
          • Dimitrios Baroutis, MD, MSc, PhD(c)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Aspirin Alone
Participants receive aspirin 160 mg orally once daily before bedtime from enrollment (<16 weeks gestation) until 36 weeks gestation.
Drug: Aspirin
Aspirin 160 mg orally once daily before bedtime. Duration: From enrollment (<16 weeks gestation) until 36 weeks gestation.
Other Names:
  • ASA
  • Acetylsalicylic acid
  • Low-dose aspirin
Experimental: Aspirin plus LMWH
Participants receive aspirin 160 mg orally once daily before bedtime PLUS weight-adjusted tinzaparin subcutaneously once daily in the morning (4,500 Anti-Xa IU for weight ≤60 kg, 6,000 Anti-Xa IU for weight 60-90 kg, 8,000 Anti-Xa IU for weight >90 kg) from enrollment (<16 weeks gestation) until 36 weeks gestation.
Drug: Aspirin
Aspirin 160 mg orally once daily before bedtime. Duration: From enrollment (<16 weeks gestation) until 36 weeks gestation.
Other Names:
  • ASA
  • Acetylsalicylic acid
  • Low-dose aspirin
Drug: Tinzaparin
Weight-adjusted tinzaparin administered subcutaneously once daily in the morning: 4,500 Anti-Xa IU/day for weight ≤60 kg, 6,000 Anti-Xa IU/day for weight 60-90 kg, and 8,000 Anti-Xa IU/day for weight >90 kg. Duration: From enrollment (<16 weeks gestation) until 36 weeks gestation.
Other Names:
  • LMWH
  • Innohep
  • Low molecular weight heparin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Preeclampsia
Time Frame: From enrollment until delivery (up to 40 weeks gestation)
Preeclampsia defined as gestational hypertension (BP ≥140/90 mmHg on at least two measurements ≥4 hours apart) after 20 weeks' gestation accompanied by one or more of: (1) Proteinuria (≥30 mg/mmol protein:creatinine ratio, ≥8 mg/mmol albumin:creatinine ratio, ≥0.3 g/24h, or ≥2+ dipstick); (2) Maternal end-organ dysfunction including neurological complications (severe headaches, visual scotomata, eclampsia, stroke, clonus), pulmonary oedema, haematological complications (platelet count <150,000/μL, disseminated intravascular coagulation, haemolysis), acute kidney injury (creatinine ≥90 μmol/L or 1 mg/dL), or liver involvement (elevated ALT or AST >40 IU/L); or (3) Uteroplacental dysfunction (fetal growth restriction, abnormal umbilical artery Doppler waveform analysis, placental abruption, angiogenic imbalance, or intrauterine fetal death), per ISSHP 2021 classification.
From enrollment until delivery (up to 40 weeks gestation)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Systemic Immune-Inflammation Index (SII)
Time Frame: At 20-24 weeks, 32-34 weeks, and 36 weeks gestation
Systemic immune-inflammation index calculated as SII = P × N/L, where P, N, and L are the peripheral blood platelet count, neutrophil count, and lymphocyte count respectively (cells per liter)
At 20-24 weeks, 32-34 weeks, and 36 weeks gestation
Incidence of Preterm Preeclampsia
Time Frame: From enrollment until 37 weeks gestation
Development of preeclampsia before 37 weeks gestation
From enrollment until 37 weeks gestation
Prevalence of placental histopathological lesions
Time Frame: At delivery
Histopathological examination of placental tissue including assessment of maternal vascular malperfusion, fetal vascular malperfusion, villous lesions, inflammatory lesions, and other pathological findings according to standardized criteria
At delivery
Soluble fms-like Tyrosine Kinase-1 (sFlt-1) Levels
Time Frame: At 20-24 weeks, 32-34 weeks, and 36 weeks gestation
Serum levels of soluble fms-like tyrosine kinase-1 (sFlt-1) measured by immunoassay
At 20-24 weeks, 32-34 weeks, and 36 weeks gestation
Placental Growth Factor (PlGF) Levels
Time Frame: At 20-24 weeks, 32-34 weeks, and 36 weeks gestation
Serum levels of placental growth factor (PlGF) measured by immunoassay
At 20-24 weeks, 32-34 weeks, and 36 weeks gestation
sFlt-1/PlGF Ratio
Time Frame: At 20-24 weeks, 32-34 weeks, and 36 weeks gestation
Ratio of soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1/PlGF ratio) measured by immunoassay
At 20-24 weeks, 32-34 weeks, and 36 weeks gestation
Interleukin-6 (IL-6) Levels
Time Frame: At 20-24 weeks, 32-34 weeks, and 36 weeks gestation
Serum levels of interleukin-6 (IL-6) measured by immunoassay
At 20-24 weeks, 32-34 weeks, and 36 weeks gestation
Incidence of Early-Onset Preeclampsia
Time Frame: From enrollment until 34 weeks gestation
Development of preeclampsia before 34 weeks gestation (early-onset preeclampsia)
From enrollment until 34 weeks gestation
Incidence of Gestational Hypertension
Time Frame: From 20 weeks gestation until delivery (up to 40 weeks)
New-onset hypertension (blood pressure ≥140/90 mmHg on two occasions at least 4 hours apart) after 20 weeks gestation without proteinuria or evidence of end-organ dysfunction
From 20 weeks gestation until delivery (up to 40 weeks)
Rate of Spontaneous Preterm Birth
Time Frame: From enrollment until delivery, assessed up to 40 weeks gestation
Spontaneous preterm labor resulting in delivery before 34 weeks gestation and before 37 weeks gestation
From enrollment until delivery, assessed up to 40 weeks gestation
Incidence of Small for Gestational Age
Time Frame: At delivery
Birth weight below the 3rd, 5th, and 10th percentile for gestational age based on standardized fetal growth charts (small for gestational age)
At delivery
Perinatal Death
Time Frame: From enrollment until 28 days after delivery
Miscarriage, intrauterine fetal death, or neonatal death within 28 days after birth attributed to preeclampsia or fetal growth restriction
From enrollment until 28 days after delivery
Neonatal Complications and Therapy
Time Frame: From delivery until hospital discharge (up to 3 months)
Composite of neonatal adverse outcomes including sepsis, intraventricular hemorrhage grade III-IV, necrotizing enterocolitis, respiratory distress syndrome (RDS), need for surfactant therapy, mechanical ventilation, blood transfusion, and admission to neonatal intensive care unit (NICU) with duration of stay
From delivery until hospital discharge (up to 3 months)
Placental Abruption
Time Frame: From enrollment until delivery (up to 40 weeks gestation)
Premature separation of the placenta from the uterine wall before delivery
From enrollment until delivery (up to 40 weeks gestation)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alexandra Hospital, Athens, Greece

Investigators

  • Study Chair: Georgios Daskalakis, PhD, First Department of Obstetrics and Gynecology, Alexandra Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 18, 2023

Primary Completion (Estimated)

August 1, 2026

Study Completion (Estimated)

July 1, 2027

Study Registration Dates

First Submitted

December 21, 2025

First Submitted That Met QC Criteria

January 15, 2026

First Posted (Actual)

January 23, 2026

Study Record Updates

Last Update Posted (Actual)

January 23, 2026

Last Update Submitted That Met QC Criteria

January 15, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 724/23-11-2022

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

The decision on individual participant data sharing will be made in accordance with institutional policies and ethical requirements. The data sharing plan will be finalized prior to study completion and publication of results.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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