Aspirin Versus Metformin in Pregnancies at High Risk of Preterm Preeclampsia: a 3-arm Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 3,000
- 试验地点
- 6
- 主要终点
- Incidence of preterm preeclampsia(<37 weeks)
研究概览
简要总结
This is a prospective, multicenter, randomized controlled, double-blind trial of three treatment arms: (1) aspirin 75 mg/day vs. (2) aspirin 150 mg/day vs. (3) aspirin 75 mg/day with metformin 1.5 g/day from the first trimester to compare the incidence of preterm preeclampsia with delivery at <37 week's gestation between the treatment arms, in order to determine the optimal therapeutic intervention for the prevention of preterm preeclampsia among Chinese women at high-risk of preeclampsia.
详细描述
All women with singleton pregnancies who are attending for their routine hospital visit at 11-13 weeks' gestation will be invited to undergo screening for preeclampsia. We use a Bayes theorem-based method that combines maternal characteristics, medical and obstetric history together with mean arterial pressure (MAP) and serum placental growth factor (PlGF) level. Women who are deemed high-risk following first trimester combined screening (cutoff corresponding to a screen positive rate of 10%, e.g ≥1 in 80) will be invited to participate in the 3-arm randomized controlled trial.
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
PI, participating research doctors, pharmacists at the local clinical trial pharmacy, project managers and others involved in the trial are all blinded to the investigational medicinal product (IMP). The tablets and capsules will be identical, so it will not be possible to distinguish between the different IMPs.
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 pregnancies
- •Live fetus at 11-13 weeks' gestation
- •High-risk for preterm preeclampsia at 11-13 weeks by the algorithm combining maternal characteristics, medical and obstetric history, MAP and serum PlGF
- •Informed and written consent
排除标准
- •Age <18 years old
- •Multiple pregnancies
- •Treatment with low-dose aspirin and metformin at the time of screening
- •Pregnancies complicated by major fetal abnormality identified during the first trimester
- •Women with learning difficulties, or serious mental illness
- •Bleeding disorders such as Von Willebrand's disease
- •Active peptic ulceration or gastrointestinal bleeding
- •Hypersensitivity to aspirin, metformin hydrochloride and other biguanides
- •Treatment with long term nonsteroidal anti-inflammatory medication
- •Hyperemesis gravidarum
- •Renal, liver or heart failure
- •A serious medical condition
- •Concurrent participation in another drug trial or at any time within the previous 28 days
- •Any other reason the clinical investigators think will prevent the potential participant from complying with the trial protocol.
研究组 & 干预措施
Aspirin 75 mg and placebo
A capsule of 75 mg aspirin plus an aspirin identical-appearing capsule of placebo to be taken orally once per night from enrolment until 36 weeks' gestation and metformin identical-appearing placebo capsules to be taken orally twice per day from enrolment until delivery.
干预措施: 75 mg acetylsalicylic acid (Drug)
Aspirin 75 mg and placebo
A capsule of 75 mg aspirin plus an aspirin identical-appearing capsule of placebo to be taken orally once per night from enrolment until 36 weeks' gestation and metformin identical-appearing placebo capsules to be taken orally twice per day from enrolment until delivery.
干预措施: Placebo of acetylsalicylic acid and Metformin (Drug)
Aspirin 150 mg and placebo
Two capsules of 75 mg aspirin to be taken orally once per night from enrolment until 36 weeks' gestation and metformin identical-appearing placebo capsules to be taken orally twice per day from enrolment until delivery.
干预措施: 150 mg acetylsalicylic acid (Drug)
Aspirin 150 mg and placebo
Two capsules of 75 mg aspirin to be taken orally once per night from enrolment until 36 weeks' gestation and metformin identical-appearing placebo capsules to be taken orally twice per day from enrolment until delivery.
干预措施: Placebo of acetylsalicylic acid and Metformin (Drug)
Aspirin 75 mg and Metformin 1.5 g
A capsule of 75 mg aspirin plus an aspirin identical-appearing capsule of placebo to be taken orally once per night from enrolment until 36 weeks' gestation and metformin capsules (up to 750 mg) to be taken twice per day from enrolment until delivery
干预措施: 75 mg acetylsalicylic acid (Drug)
Aspirin 75 mg and Metformin 1.5 g
A capsule of 75 mg aspirin plus an aspirin identical-appearing capsule of placebo to be taken orally once per night from enrolment until 36 weeks' gestation and metformin capsules (up to 750 mg) to be taken twice per day from enrolment until delivery
干预措施: 1.5g Metformin (Drug)
结局指标
主要结局
Incidence of preterm preeclampsia(<37 weeks)
时间窗: ≥20 weeks to <37 weeks of gestation
Preeclampsia will be defined as per the International Society for the Study of Hypertension in Pregnancy.The Proportions of delivery with preterm-preeclampsia between different intervention groups will be measured.
次要结局
- Neonatal morbidity(During the first 28 days of life (0-27days))
- Adverse outcome of pregnancy at <37 weeks.(<37 weeks of gestation)
- Adverse outcome of pregnancy at <34 weeks.(<34 weeks of gestation)
- Neonatal mortality(During the first 28 days of life (0-27days))
- Adverse outcome of pregnancy at ≥37 weeks(≥37 weeks of gestation)
- Neonatal birthweight below the 3rd,5th and 10th centile.(At delivery)
- <34 weeks and <37 weeks spontaneous preterm delivery(At spontaneous delivery)
- Gestational age(At delivery)
- Stillbirth or neonatal death(At delivery)
研究者
Chiu Yee Liona Poon
Professor (Clinical)
Chinese University of Hong Kong