Aspirin Versus Metformin in Pregnancies at High Risk of Preterm Preeclampsia: a 3-arm Randomized Controlled Trial

Aspirin Versus Metformin in Pregnancies at High Risk of Preterm Preeclampsia: a 3-arm Randomized Controlled Trial

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.

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.

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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.