A Phase 4 interventional study of Aspirin and Tinzaparin in Preeclampsia Severe, Toxemia Of Pregnancy and Preeclampsia, sponsored by Alexandra Hospital, Athens, Greece. Recruiting at 1 site in Greece. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-01-23.
Sponsored by Alexandra Hospital, Athens, Greece · Phase 4, Interventional, and Prevention
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.
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.
916 studies on the registry are indexed under Pre-Eclampsia; 243 are open to participants now.
This study's planned enrollment of 100 is close to the median of 110 across 480 interventional studies indexed under Pre-Eclampsia.
Browse Pre-Eclampsia studies →Alexandra Hospital, Athens, Greece is the lead sponsor of 8 studies on the registry; 1 is open to participants now.
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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.
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.
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.
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.
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.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
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.
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.
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.
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.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants receive aspirin 160 mg orally once daily before bedtime from enrollment (\<16 weeks gestation) until 36 weeks gestation.
Drug: Aspirin
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 · Drug: Tinzaparin
Aspirin 160 mg orally once daily before bedtime. Duration: From enrollment (\<16 weeks gestation) until 36 weeks gestation.
Also known as: ASA, Low-dose aspirin, Acetylsalicylic acid
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.
Also known as: Low molecular weight heparin, Innohep, LMWH
Incidence of Preeclampsia
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.
Time frame: From enrollment until delivery (up to 40 weeks gestation)
Systemic Immune-Inflammation Index (SII)
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)
Time frame: At 20-24 weeks, 32-34 weeks, and 36 weeks gestation
Incidence of Preterm Preeclampsia
Development of preeclampsia before 37 weeks gestation
Time frame: From enrollment until 37 weeks gestation
Prevalence of placental histopathological lesions
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
Time frame: At delivery
Soluble fms-like Tyrosine Kinase-1 (sFlt-1) Levels
Serum levels of soluble fms-like tyrosine kinase-1 (sFlt-1) measured by immunoassay
Time frame: At 20-24 weeks, 32-34 weeks, and 36 weeks gestation
Placental Growth Factor (PlGF) Levels
Serum levels of placental growth factor (PlGF) measured by immunoassay
Time frame: At 20-24 weeks, 32-34 weeks, and 36 weeks gestation
sFlt-1/PlGF Ratio
Ratio of soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1/PlGF ratio) measured by immunoassay
Time frame: At 20-24 weeks, 32-34 weeks, and 36 weeks gestation
Interleukin-6 (IL-6) Levels
Serum levels of interleukin-6 (IL-6) measured by immunoassay
Time frame: At 20-24 weeks, 32-34 weeks, and 36 weeks gestation
Incidence of Early-Onset Preeclampsia
Development of preeclampsia before 34 weeks gestation (early-onset preeclampsia)
Time frame: From enrollment until 34 weeks gestation
Incidence of Gestational Hypertension
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
Time frame: From 20 weeks gestation until delivery (up to 40 weeks)
Rate of Spontaneous Preterm Birth
Spontaneous preterm labor resulting in delivery before 34 weeks gestation and before 37 weeks gestation
Time frame: From enrollment until delivery, assessed up to 40 weeks gestation
Incidence of Small for Gestational Age
Birth weight below the 3rd, 5th, and 10th percentile for gestational age based on standardized fetal growth charts (small for gestational age)
Time frame: At delivery
Perinatal Death
Miscarriage, intrauterine fetal death, or neonatal death within 28 days after birth attributed to preeclampsia or fetal growth restriction
Time frame: From enrollment until 28 days after delivery
Neonatal Complications and Therapy
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
Time frame: From delivery until hospital discharge (up to 3 months)
Placental Abruption
Premature separation of the placenta from the uterine wall before delivery
Time frame: From enrollment until delivery (up to 40 weeks gestation)
Plan to share: Undecided — 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.
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Studies of the drug tested here: Tinzaparin
Alexandra Hospital, Athens, Greece