Low Molecular Weight Heparin for the Treatment of Early Fetal Growth Restriction
试验速览
- 阶段
- 3 期
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Gestational age at delivery
研究概览
简要总结
Early fetal growth restriction (FGR) is associated with considerable fetal and neonatal morbimortality. Placental thrombosis, infarcts and hypercoagulability are frequently seen in these pregnancies, suggesting a role for the activation of the coagulation cascade in the genesis of FGR. Patients will be randomized for low-molecular weight heparin or standard of care, and the outcomes of both arms (gestational age at delivery, gestational and fetal morbidity) will be compared.
详细描述
FGR is the second leading cause of perinatal mortality, being associated with approximately 30% of stillbirths. Early FGR is associated with substantial disturbances of placental implantation and fetal hypoxia, which requires fetal cardiovascular adaptation. Both maternal and fetal Doppler alterations are present, allowing for risk stratification and monitoring. Although the precise etiology for FGR due to placental causes is unknown, placental thrombosis, infarcts and hypercoagulability are frequently seen, suggesting a role for the activation of the coagulation cascade in the genesis of FGR. Currently, the management of early FGR is limited to the monitoring of fetal Doppler parameters until the risks for preterm delivery outweight the benefits of ongoing monitoring. As such, there is a special need for effective preventive and therapeutic interventions that improve the outcomes. Low molecular weight heparin (LMWH), for its anticoagulant and anti-inflammatory properties has been suggested as a possible therapeutic agent in this setting. The investigators will randomize the participants to two intervention arms in a one-to-one ratio, using a computer generated randomization program. The randomization will be stratified for gestational age at diagnosis of FGR (22 to 26 weeks and >26 to 32 weeks). The experimental group will be administered enoxaparin subcutaneous injections (40 mg, 4000 IU daily) and the control group will be provided standard of care. Both groups will start intervention immediately after the diagnosis of FGR, and will continue it until 36 weeks of gestation or 12 hours before delivery, whichever comes first.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Care Provider, Outcomes Assessor)
盲法说明
Blinded to clinicians performing the ultrasound and outcomes assessor
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
- •being 18 years old or older
- •being able to provide consent
- •having a viable singleton pregnancy with diagnosed early FGR confirmed in our unit according to the 2020 International Society of Ultrasound in Obstetrics & Gynecology (ISUOG) criteria (one solitary parameter: estimated fetal weight/ abdominal circumference lower than the 3rd centile or absent end-diastolic flow in umbilical artery; or estimated fetal weight/abdominal circumference below the 10th centile combined with either umbilical artery pulsatility index > 95th centile or uterine artery mean pulsatility index > 95th centile)
排除标准
- •multiple gestation;
- •diagnosed fetal chromosomal abnormalities;
- •associated fetal morphological malformations;
- •evidence of fetal infection (serological or after invasive testing);
- •use of LMWH or NFH in the index pregnancy before randomization or start of any of these medications for another indication if the patient is in the control group
- •present use of systemic salicylates in anti-inflammatory dosage (> 150mg/day) or NSAIDs (including ketorolac)
- •maternal history of allergy to LMWH or non-fractionated heparin (NFH);
- •hypersensitivity to pork products;
- •maternal history of heparin-induced thrombocytopenia;
- •maternal thrombocytopenia (platelets < 100 000);
- •history of maternal hemophilia or Von Willebrand disease
- •presence of placental hematoma;
- •maternal diabetic retinopathy;
- •bacterial endocarditis;
- •active clinically significant bleeding and conditions with a high risk of hemorrhage, including recent hemorrhagic stroke, gastrointestinal ulcer, presence of malignant neoplasm at high risk of bleeding, recent brain, spinal or ophthalmic surgery, known or suspected esophageal varices, arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities;
- •persistent blood pressure > 160/100 mmHg, despite optimal anti-hypertensive regimen;
- •history of severe renal disease (eGFR <30mL/min);
- •known or suspected hepatic impairment;
- •current participation in another clinical trial;
- •patients that are not part of the national health system (SNS);
- •delivery already scheduled, or predicted in the next 7 days.
研究组 & 干预措施
Intervention group, enoxaparin
Enoxaparin subcutaneous injections
干预措施: subcutaneous Enoxaparin (Drug)
Standard of care
Obsteric standard of care
干预措施: standard of care (Other)
结局指标
主要结局
Gestational age at delivery
时间窗: day of delivery
Best assessment of the time of gestation, either by first trimester sonography, last menstrual day or day of implantation of in vitro conception product
次要结局
- Neonatal birtweight and birthweight centile(day of delivery)
- Stillbirth, neonatal intensive care admission and duration of admission(from randomization up to 1 year after delivery)
- Maternal and fetal Doppler parameters(from randomization to delivery)
- Placental pathology(day of delivery)
- Sflt1-PLGF ratio(from randomization to delivery)
- Syncytiotrophoblast membrane extracellular vesicles (STB-EV)(from randomization up to 1 week after delivery)
- Gestational hypertension or preeclampsia; placental abruption(from randomization up to 1 week after delivery)
- Antepartum hemorrhage; maternal thrombocytopenia (platelets < 100 000 x 10 9/L); postpartum hemorrhage(from randomization up to 1 week after delivery)
- Mode and indication for delivery(from randomization up to 48h after delivery)
- Newborn Apgar Score in the 5th minute(day of delivery)
- Newborn Umbilical Artery pH(day of delivery)