A Dose Escalation Study of Low Dose Aspirin for the Prevention of Recurrent Preterm Birth
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 1,800
- 试验地点
- 27
- 主要终点
- Rate of recurrent preterm delivery or fetal death prior to 35 weeks 0 days gestation
研究概览
简要总结
This is a phase-III multi-center double-blind randomized clinical trial of 1,800 individuals with a history of prior preterm birth at less than 35 weeks gestation who are randomized to either 162 mg aspirin or 81 mg aspirin daily. The study drug will be initiated between 10 and 15 weeks gestation and continued through 36 weeks, 6 days gestation. The primary endpoint is recurrent preterm delivery or fetal death prior to 35 weeks, 0 days gestation.
详细描述
This is a phase-III multi-center double-blind randomized clinical trial of 1,800 individuals with a history of prior preterm birth at less than 35 weeks gestation who are randomized to either 162 mg aspirin or 81 mg aspirin daily.
The primary objective is to assess the efficacy of daily 162 mg of aspirin compared to 81 mg aspirin in reducing recurrent preterm delivery or fetal death before 35 weeks, 0 days gestation in individuals with a proximal birth between 20 weeks, 0 days and 34 weeks, 6 days gestation with spontaneous preterm delivery (sPTB), ischemic placental disease (IPD), or stillbirth. Ischemic placental disease includes small for gestational age, preeclampsia, or placental abruption.
The secondary objective is to assess the efficacy of daily 162 mg of aspirin compared to 81 mg aspirin in reducing ischemic placental disease in individuals with a proximal birth between 20 weeks, 0 days and 34 weeks, 6 days gestation with sPTB, IPD, or stillbirth.
Tertiary /Exploratory objectives are 1) to assess the efficacy of daily 162 mg of aspirin compared to 81 mg aspirin in reducing adverse maternal and neonatal outcomes, and 2) to assess maternal and neonatal safety in individuals with a proximal birth between 20 weeks, 0 days and 34 weeks, 6 days gestation with sPTB, IPD, or stillbirth.
Individuals will be randomized between 10 and 15 weeks gestation to either 162mg or 81mg of aspirin daily and continue the study intervention through 36 weeks, 6 days gestation. Participants will have monthly virtual or in-person visits through 37 weeks gestation to assess study intervention compliance, side effects, medication use, and unscheduled hospitalization. Maternal blood will be collected in a subset of the population. Research staff will abstract maternal and neonatal outcomes following delivery and discharge from the hospital.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The study intervention is packaged and shipped from the central distribution center to the clinical sites. Participants, clinical staff, and clinical site investigators and research staff are masked to the study intervention.
入排标准
- 年龄范围
- 14 Years 至 —（Child, Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •14 years or older
- •Singleton gestation. Twin gestation reduced to a singleton, either spontaneously or therapeutically, is not eligible unless the reduction occurred before 13 weeks 6 days project gestational age. Higher-order multifetal gestations reduced to singletons are not eligible.
- •Gestational age at randomization between 10 weeks 0 days and 15 weeks 6 days based on clinical information and evaluation of the earliest ultrasound.
- •Prior preterm birth between 20 weeks 0 days and 34 weeks 6 days with one of the following in the proximal birth reaching 20 weeks or greater:
- •Spontaneous preterm birth is defined as spontaneous preterm labor or premature rupture of membranes
- •Ischemic placental disease is defined as preeclampsia, small for gestational age, fetal growth restriction, or placental abruption, as defined clinically.
- •Stillbirth excluding those with known genetic disorders or major congenital anomalies.
排除标准
- •Known allergy or hypersensitivity to aspirin or any medical condition where aspirin is contraindicated (e.g., history of peptic ulcer disease, nasal polyps, NSAID-induced asthma, history of gastrointestinal bleeding, known G6PD deficiency, severe hepatic dysfunction, bleeding disorders, and consumption of 3 or more alcoholic drinks per day)
- •Taking other anticoagulants such as Heparin or Low-Molecular weight Heparin
- •Thrombocytopenia defined as a platelet count defined as a platelet count <100,000 microliters
- •Gastric bypass surgery, regardless of type
- •Aspirin use >81 mg daily during the current pregnancy who are not willing or able to go through a 2-week washout before randomization.
- •Known major Mullerian anomaly of the uterus (specifically bicornuate, unicornuate, or uterine septum not resected) due to increased risk of preterm delivery.
- •Known fetal genetic disease or major malformations
- •Fetal demise or planned termination of pregnancy. Selective reduction by 13 weeks 6 days gestation, from twins to singleton, is not an exclusion.
- •Any fetal/maternal condition requiring invasive in-utero assessment or treatment, for example, significant red cell antigen sensitization or neonatal alloimmune thrombocytopenia.
- •Patients with any of the following medical conditions because of increased risk for adverse pregnancy outcome or indicated preterm birth:
- •Treated hypertension requiring more than one agent
- •Chronic renal disease with baseline serum creatinine ≥1.5 mg/dL
- •Conditions treated with chronic oral glucocorticoid therapy (e.g., systemic lupus erythematosus)
- •Uncontrolled hyper- and hypothyroid disease
- •New York Heart Association (NYHA) stage II or greater cardiac disease
- •Planned indicated delivery prior to 37 weeks.
- •Participation in another interventional study that influences the primary outcome in this study (gestational age at delivery).
- •Participation in this trial in a previous pregnancy.
- •Delivery planned at a non-participating site
研究组 & 干预措施
162mg Aspirin Daily
One 81mg capsule of aspirin daily through 36 weeks 6 days gestation.
干预措施: 162mg Aspirin (Drug)
81mg Aspirin Daily
Two 81mg capsules of aspirin daily through 36 weeks 6 days gestation.
干预措施: 81mg Aspirin (Drug)
结局指标
主要结局
Rate of recurrent preterm delivery or fetal death prior to 35 weeks 0 days gestation
时间窗: Between randomization and 35 weeks, 0 days gestation (a period of up to 25 weeks)
Number and rate of participants who experience a recurrent preterm delivery or fetal death before 35 weeks, 0 days gestation.
次要结局
- Rate of ischemic placental disease(Between randomization and delivery (a period of up to 32 weeks))