Clinical trial NCT05580523: Aspirin Versus Metformin in Pregnancies at High Risk of Preterm Preeclampsia: a 3-arm Randomized Controlled Trial
Official title: Aspirin Versus Metformin in Pregnancies at High Risk of Preterm Preeclampsia: a 3-arm Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Preeclampsia
Keywords: Preterm preeclampsia
Aspirin
Metformin
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
Collaborators: name: Obstetrics & Gynecology Hospital of Fudan University
name: Shanghai First Maternity and Infant Hospital
name: West China Second University Hospital
name: Peking University First Hospital
First posted: 2022-10-14
Enrollment: 3000
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of preterm preeclampsia(<37 weeks)
timeFrame: ≥20 weeks to <37 weeks of gestation
Secondary outcomes:
measure: Adverse outcome of pregnancy at <37 weeks.
timeFrame: <37 weeks of gestation
measure: Adverse outcome of pregnancy at <34 weeks.
timeFrame: <34 weeks of gestation
measure: Adverse outcome of pregnancy at ≥37 weeks
timeFrame: ≥37 weeks of gestation
measure: Neonatal mortality
timeFrame: During the first 28 days of life (0-27days)
measure: Neonatal morbidity
timeFrame: During the first 28 days of life (0-27days)
measure: Neonatal birthweight below the 3rd,5th and 10th centile.
timeFrame: At delivery
measure: Stillbirth or neonatal death
timeFrame: At delivery
measure: <34 weeks and <37 weeks spontaneous preterm delivery
timeFrame: At spontaneous delivery
measure: Gestational age
timeFrame: At delivery
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Guangzhou
country: China
facility: Guangzhou Women and Children's Medical Center
state: Guangdong
city: Guangzhou
country: China
facility: The Third Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Shanghai
country: China
facility: Obstetrics and Gynecology Hospital of Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Shanghai First Maternity and Infant Hospital
state: Shanghai
city: Chengdu
country: China
facility: West China Second University Hospital, Sichuan University
state: Sichuan
Study officials:
affiliation: Chinese University of Hong Kong
name: Chiu Yee, Liona Poon, MD
role: PRINCIPAL_INVESTIGATOR
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