Combined Administration of Low Molecular Weight Heparin and Aspirin Versus Aspirin Alone in Gravidas at High Risk for Preeclampsia: A Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Incidence of Preeclampsia
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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)
研究组 & 干预措施
Aspirin Alone
Participants receive aspirin 160 mg orally once daily before bedtime from enrollment (<16 weeks gestation) until 36 weeks gestation.
干预措施: Aspirin (Drug)
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.
干预措施: Aspirin (Drug)
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.
干预措施: Tinzaparin (Drug)
结局指标
主要结局
Incidence of Preeclampsia
时间窗: 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.
次要结局
- Systemic Immune-Inflammation Index (SII)(At 20-24 weeks, 32-34 weeks, and 36 weeks gestation)
- Incidence of Preterm Preeclampsia(From enrollment until 37 weeks gestation)
- Prevalence of placental histopathological lesions(At delivery)
- Soluble fms-like Tyrosine Kinase-1 (sFlt-1) Levels(At 20-24 weeks, 32-34 weeks, and 36 weeks gestation)
- Placental Growth Factor (PlGF) Levels(At 20-24 weeks, 32-34 weeks, and 36 weeks gestation)
- sFlt-1/PlGF Ratio(At 20-24 weeks, 32-34 weeks, and 36 weeks gestation)
- Interleukin-6 (IL-6) Levels(At 20-24 weeks, 32-34 weeks, and 36 weeks gestation)
- Incidence of Early-Onset Preeclampsia(From enrollment until 34 weeks gestation)
- Incidence of Gestational Hypertension(From 20 weeks gestation until delivery (up to 40 weeks))
- Rate of Spontaneous Preterm Birth(From enrollment until delivery, assessed up to 40 weeks gestation)
- Incidence of Small for Gestational Age(At delivery)
- Perinatal Death(From enrollment until 28 days after delivery)
- Neonatal Complications and Therapy(From delivery until hospital discharge (up to 3 months))
- Placental Abruption(From enrollment until delivery (up to 40 weeks gestation))
研究者
Georgios Daskalakis
Professor of Obstetrics and Gynecology
Alexandra Hospital, Athens, Greece