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

The Chinese University of Hong Kong

Status: Enrolling

Conditions: Preeclampsia

Treatments: Drug: 1.5g Metformin; Drug: 75 mg acetylsalicylic acid; Drug: 150 mg acetylsalicylic acid; Drug: Placebo of acetylsalicylic acid and Metformin

Study type: Interventional

Funder types: Other

Identifiers

NCT05580523

MOST-AVERT

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 3,000 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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3,000 participants in 3 patient groups

Aspirin 75 mg and placebo

Experimental group

Description:

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.

Treatment:

Drug: Placebo of acetylsalicylic acid and Metformin

Drug: 75 mg acetylsalicylic acid

Aspirin 150 mg and placebo

Experimental group

Description:

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.

Treatment:

Drug: Placebo of acetylsalicylic acid and Metformin

Drug: 150 mg acetylsalicylic acid

Aspirin 75 mg and Metformin 1.5 g

Experimental group

Description:

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

Treatment:

Drug: 75 mg acetylsalicylic acid

Drug: 1.5g Metformin