NCT Number: NCT07361679
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.
Interested in participating?
Request Info18 year and older
Female
Interventional
Phase 4
Athens, Attica, 11528, Greece
Location status: Recruiting
Dimitrios Baroutis, MD, MSc, PhD(c)
CONTACT
Dimitrios Baroutis, MD, MSc, PhD(c)
PRINCIPAL_INVESTIGATOR
Georgios Daskalakis, MD, PhD
CONTACT
Georgios Daskalakis, MD, PhD
PRINCIPAL_INVESTIGATOR
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.
Healthy volunteers accepted: No
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
Exclusion criteria
Aspirin 160 mg orally once daily before bedtime. Duration: From enrollment (<16 weeks gestation) until 36 weeks gestation.
Other names: 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.
Other names: Low molecular weight heparin, Innohep, LMWH
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.
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)
Time frame: From enrollment until 37 weeks gestation
Development of preeclampsia before 37 weeks gestation
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
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
Time frame: At 20-24 weeks, 32-34 weeks, and 36 weeks gestation
Serum levels of placental growth factor (PlGF) measured by immunoassay
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
Time frame: At 20-24 weeks, 32-34 weeks, and 36 weeks gestation
Serum levels of interleukin-6 (IL-6) measured by immunoassay
Time frame: From enrollment until 34 weeks gestation
Development of preeclampsia before 34 weeks gestation (early-onset preeclampsia)
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
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
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)
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
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
Time frame: From enrollment until delivery (up to 40 weeks gestation)
Premature separation of the placenta from the uterine wall before delivery
Contact information is provided by the study sponsor or research team.
Alexandra Hospital, Athens, Greece
Other
Combined Administration of Low Molecular Weight Heparin and Aspirin Versus Aspirin Alone in Gravidas at High Risk for Preeclampsia: A Randomized Controlled Trial
Acronym: preGO
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