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

November 5, 2023 updated by: Chiu Yee Liona Poon, Chinese University of Hong Kong
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

3000

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China
        • Recruiting
        • Peking University First Hospital
        • Contact:
        • Contact:
    • Guangdong
      • Guangzhou, Guangdong, China
        • Withdrawn
        • Guangzhou Women and Children's Medical Center
      • Guangzhou, Guangdong, China
        • Not yet recruiting
        • The Third Affiliated Hospital of Guangzhou Medical University
        • Contact:
        • Contact:
    • Shanghai
      • Shanghai, Shanghai, China
        • Recruiting
        • Shanghai first maternity and infant hospital
        • Contact:
        • Contact:
      • Shanghai, Shanghai, China
    • Sichuan
      • Chengdu, Sichuan, China
        • Recruiting
        • West China Second University Hospital, Sichuan University
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: 75 mg acetylsalicylic acid
75 mg acetylsalicylic acid (C9H8O4, CAS number 50-78-2) daily, Oral
Other Names:
  • 75mg Aspirin
Drug: Placebo of acetylsalicylic acid and Metformin
Pills with shape, color and smell same with acetylsalicylic acid and metformin, daily, oral
Experimental: 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.
Drug: Placebo of acetylsalicylic acid and Metformin
Pills with shape, color and smell same with acetylsalicylic acid and metformin, daily, oral
Drug: 150 mg acetylsalicylic acid
150 mg acetylsalicylic acid (C9H8O4, CAS number 50-78-2) daily, Oral
Other Names:
  • 150mg Aspirin
Experimental: 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
Drug: 75 mg acetylsalicylic acid
75 mg acetylsalicylic acid (C9H8O4, CAS number 50-78-2) daily, Oral
Other Names:
  • 75mg Aspirin
Drug: 1.5g Metformin
up to 1.5 g metformin (C4H11N5, CAS number 657-24-9) daily, Oral Dose increases from 0.5g to 1.0g to 1.5g
Other Names:
  • 1.5g Glucophage

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of preterm preeclampsia(<37 weeks)
Time Frame: ≥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.
≥20 weeks to <37 weeks of gestation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse outcome of pregnancy at <37 weeks.
Time Frame: <37 weeks of gestation
including preeclampsia requiring delivery, gestational age (SGA; <5th percentile) requiring delivery, miscarriage or still birth or placental abruption.
<37 weeks of gestation
Adverse outcome of pregnancy at <34 weeks.
Time Frame: <34 weeks of gestation
including preeclampsia requiring delivery, gestational age (SGA; <5th percentile) requiring delivery, miscarriage or still birth or placental abruption.
<34 weeks of gestation
Adverse outcome of pregnancy at ≥37 weeks
Time Frame: ≥37 weeks of gestation
including preeclampsia requiring delivery, gestational age (SGA; <5th percentile) requiring delivery, stillbirth or placental abruption.
≥37 weeks of gestation
Neonatal mortality
Time Frame: During the first 28 days of life (0-27days)
A neonatal death is a death during 0-27 days of life.
During the first 28 days of life (0-27days)
Neonatal morbidity
Time Frame: During the first 28 days of life (0-27days)
Composite neonatal morbidity (any one of the following): >grade II intra-ventricular hemorrhage; neonatal sepsis confirmed by cultures; neonatal anemia requiring transfusion; respiratory distress syndrome requiring surfactant and ventilation; necrotising enterocolitis requiring surgical intervention.
During the first 28 days of life (0-27days)
Neonatal birthweight below the 3rd,5th and 10th centile.
Time Frame: At delivery
Birthweight and birthweight percentile for gestational age at delivery is calculated using a normal range derived in a Chinese population.
At delivery
<34 weeks and <37 weeks spontaneous preterm delivery
Time Frame: At spontaneous delivery
Spontaneous delivery at <34 weeks(early preterm) and at <37 weeks(total preterm) includes those with spontaneous onset of labor and those with preterm pre-labor rupture of membranes (PPROM).
At spontaneous delivery
Stillbirth or neonatal death
Time Frame: At delivery
Stillbirth: the death of a baby before or during birth after 24 weeks of gestation. Neonatal death: the death of a baby within the first 28 days of life.
At delivery
Gestational age
Time Frame: At delivery
Gestation is the period of time between conception and birth. During this time, the baby grows and develops inside the mother's womb. Gestational age is the common term used during pregnancy to describe how far along the pregnancy is. It is measured in weeks, from the first day of the woman's last menstrual cycle to the current date. A normal pregnancy can range from 38 to 42 weeks.
At delivery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chinese University of Hong Kong

Collaborators

Peking University First Hospital
Obstetrics & Gynecology Hospital of Fudan University
Shanghai First Maternity and Infant Hospital
West China Second University Hospital

Investigators

  • Principal Investigator: Chiu Yee, Liona Poon, MD, Chinese University of Hong Kong

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 3, 2023

Primary Completion (Estimated)

January 1, 2025

Study Completion (Estimated)

November 30, 2025

Study Registration Dates

First Submitted

October 12, 2022

First Submitted That Met QC Criteria

October 13, 2022

First Posted (Actual)

October 14, 2022

Study Record Updates

Last Update Posted (Actual)

November 8, 2023

Last Update Submitted That Met QC Criteria

November 5, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MOST-AVERT

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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