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

Alexandra Hospital, Athens, Greece

Status and phase: Enrolling; Phase 4

Conditions: Hypertension, Pregnancy-Induced; Pregnancy Complications; Preeclampsia Severe; Preeclampsia; Gestational Hypertension; Toxemia Of Pregnancy

Treatments: Drug: Aspirin; Drug: Tinzaparin

Study type: Interventional

Funder types: Other

Identifiers

NCT07361679

724/23-11-2022

Details and patient eligibility

About

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.

Full 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.

Enrollment: 100 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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100 participants in 2 patient groups

Aspirin Alone

Active Comparator group

Description:

Participants receive aspirin 160 mg orally once daily before bedtime from enrollment (\<16 weeks gestation) until 36 weeks gestation.

Treatment:

Drug: Aspirin

Aspirin plus LMWH

Experimental group

Description:

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.

Treatment:

Drug: Tinzaparin

Drug: Aspirin