A Multicenter, Open-label, Randomized, Controlled, Phase 2 Trial Evaluating Whether Low Molecular Heparin Could Improve Pregnancy Outcomes With Protein S Deficiency
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Rate of livebirth
研究概览
简要总结
To evaluate whether low molecular heparin could improve pregnancy outcomes in pregnancies with protein S deficiency.
详细描述
This is a parallel-group, multicenter, randomized controlled trial of 48 pregnancies with protein S deficiency in China. Patients are randomized into three groups to receive enoxaparin combined with aspirin, aspirin alone and no intervention. The primary outcome measure is livebirth rate.
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 50 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Plasma activity levels of PS when not pregnant are below the lower limits of the adult reference values (generally about 60-70% for PS) without the use of warfarin. Or, free protein S antigen levels in the second and third trimesters are less than 30% and less than 24%, respectively
- •Pregnant women who delivered from Aug 1st, 2024 to Oct 15th, 2027
- •One or more family members exhibiting the same symptoms as the patient
- •Past history of early onset thrombosis (age 50 or below)
- •Repeated recurrence of thrombosis
- •Thromboses in unusual sites
- •New onset of thrombosis during current pregnancy or after delivery
- •Patients with diagnosis confirmed by gene analysis Inclusion criteria 1 and 2 must always be met regardless of items of 3-
- •Written informed consent
排除标准
- •Thrombophilia other than Protein S deficiency
- •Antiphospholipid syndrome, systemic lupus erythematosus, platelet abnormalities, vascular disorders, blood flow obstruction, paroxysmal nocturnal hemoglobinuria, malignant tumor and other conditions that tend to cause thrombosis
- •Allergy/hypersensitivity to enoxaparin or aspirin
- •Heparin-associated thrombocytopenia or thrombocytopenia (platelet count<75 × 10^9/L)
- •Organ lesions at risk for bleeding such as acute stomach/bowel ulcers, cerebral hemorrhage, cerebral aneurysm
- •uncontrolled hypertension or Severe hypertension (Systolic Blood Pressure >200mmhg and/or Diastolic Blood Pressure >120mmHg)
- •Severe hepatic failure (INR >1.8)
- •Serum creatinine greater than 80 umol/L (1.3mg/dl) and an abnormal 24 hour urine creatine clearance (<30ml/min)
- •Abnormal uterine cavity on hysterosalpingogram/hysteroscopy
研究组 & 干预措施
The combination group
Subjects randomized to the combination group will receive daily injections of enoxaparin at a dose of 4000 IU and aspirin 75mg per day orally until delivery.
干预措施: Enoxaparin (Drug)
The combination group
Subjects randomized to the combination group will receive daily injections of enoxaparin at a dose of 4000 IU and aspirin 75mg per day orally until delivery.
干预措施: Aspirin (Drug)
The Aspirin group
Aspirin will be given at a dose of 75mg, orally, each day until delivery.
干预措施: Aspirin (Drug)
All groups
Participants in all groups will receive daily injections of enoxaparin at a dose of 4000 IU within 6 weeks at postpartum.
干预措施: Enoxaparin (Drug)
结局指标
主要结局
Rate of livebirth
时间窗: From date of randomization until delivery, assessed up to 42 months
Incidents of livebirth
次要结局
- Parameters of maternal coagulation-related indicators(From the start of study treatment to 6 weeks post-partum)
- Incidents of placental insufficiency(up to 6 weeks post-partum)
- Other incidents of adverse pregnancy outcomes(up to 37 weeks)
- Neonatal Data(after the delivery (an expected average of one month))
- Parameters to assess the safety of low molecular heparin(From the start of study treatment to 6 weeks post-partum)
- Incidents of thrombosis/thromboembolism(From the start of study treatment to 6 weeks post-partum)
研究者
Xiao Hui Zhang
Vice president of Peking University Institute of Hematology
Peking University People's Hospital