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PreeclampsiaNCT05580523

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

A study testing 75 mg acetylsalicylic acid, 1.5g Metformin and 150 mg acetylsalicylic acid in people with Preeclampsia, run by Chinese University of Hong Kong at 6 sites in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Preeclampsia
What is being tested?
75 mg acetylsalicylic acid, 1.5g Metformin and 150 mg acetylsalicylic acid
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
3,000 participants
Where
6 sitesChina
Study dates
3 Jul 2023to 30 Nov 2025
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 14Show fewer
  • 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 locations and contacts

6 sites in 1 country.

Chiu Yee, Liona Poon, MD contact

(852) 3505 1290

liona.poon@cuhk.edu.hk

Chi Chiu Wang, PhD contact

(852) 3505 3099

ccwang@cuhk.edu.hk

6 sites in 1 country

China6 sites, 5 recruiting
  • Peking University First Hospital

    Beijing, Beijing Municipality

    Xueyin Wang, PhD, +86-1083573227, xueyin0925@163.com

    Yuchun Zhu, MD, +86-13911102732, zhu_yuchun@163.com

    Recruiting
  • West China Second University Hospital, Sichuan University

    Chengdu, Sichuan

    Yanping Zhang, MD, 18280173971, 1187256353@qq.com

    Rong Zhou, MD, 18180609085, zhourong_hx@scu.edu.cn

    Recruiting
  • Guangzhou Women and Children's Medical Center

    Guangzhou, Guangdong

    Withdrawn
  • The Third Affiliated Hospital of Guangzhou Medical University

    Guangzhou, Guangdong

    Zhihua Li, MD, 18998321631, zhihuali2004@163.com

    Dunjin Chen, MD, 18928916722, gzdrchen@gzhmc.edu.cn

    Not yet recruiting
  • Obstetrics and Gynecology Hospital of Fudan University

    Shanghai, Shanghai Municipality

    Weirong Gu, MD,PhD, +86-13501674753, guweirong1237@fckyy.org.cn

    Qiongjie Zhou, MD,PhD, +86-13671558865, zhouqiongjie1732@fckyy.org.cn

    Recruiting
  • Shanghai First Maternity and Infant Hospital

    Shanghai, Shanghai Municipality

    Hao Ying, MD, +86 13371985049, stephenying_2011@163.com

    Xiang Jiang, MD, +86 18502129988, jiangxiang79@163.com

    Recruiting

Other trials in China

About this study

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.

Read the 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.

Conditions
Preeclampsia
Being tested
75 mg acetylsalicylic acid, 1.5g Metformin, 150 mg acetylsalicylic acid, Placebo of acetylsalicylic acid and Metformin
Keywords
Preterm preeclampsia, Aspirin, Metformin
Medical subject headings
Pre-Eclampsia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 75 mg acetylsalicylic acidDrug

    Also called 75mg Aspirin

    75 mg acetylsalicylic acid (C9H8O4, CAS number 50-78-2) daily, Oral

  • 1.5g MetforminDrug

    Also called 1.5g Glucophage

    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

  • 150 mg acetylsalicylic acidDrug

    Also called 150mg Aspirin

    150 mg acetylsalicylic acid (C9H8O4, CAS number 50-78-2) daily, Oral

  • Placebo of acetylsalicylic acid and MetforminDrug

    Pills with shape, color and smell same with acetylsalicylic acid and metformin, daily, oral

Study groups in NCT05580523
Study groupRoleWhat they receive
Aspirin 75 mg and placeboExperimentalA 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.
Receives: Drug: 75 mg acetylsalicylic acid; Drug: Placebo of acetylsalicylic acid and Metformin
Aspirin 150 mg and placeboExperimentalTwo 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.
Receives: Drug: 150 mg acetylsalicylic acid; Drug: Placebo of acetylsalicylic acid and Metformin
Aspirin 75 mg and Metformin 1.5 gExperimentalA 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
Receives: Drug: 75 mg acetylsalicylic acid; Drug: 1.5g Metformin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of preterm preeclampsia(<37 weeks)

    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.

    Measured: ≥20 weeks to <37 weeks of gestation

Secondary outcomes (9)
  1. Adverse outcome of pregnancy at <37 weeks.

    including preeclampsia requiring delivery, gestational age (SGA; <5th percentile) requiring delivery, miscarriage or still birth or placental abruption.

    Measured: <37 weeks of gestation

  2. Adverse outcome of pregnancy at <34 weeks.

    including preeclampsia requiring delivery, gestational age (SGA; <5th percentile) requiring delivery, miscarriage or still birth or placental abruption.

    Measured: <34 weeks of gestation

  3. Adverse outcome of pregnancy at ≥37 weeks

    including preeclampsia requiring delivery, gestational age (SGA; <5th percentile) requiring delivery, stillbirth or placental abruption.

    Measured: ≥37 weeks of gestation

  4. Neonatal mortality

    A neonatal death is a death during 0-27 days of life.

    Measured: During the first 28 days of life (0-27days)

  5. Neonatal morbidity

    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.

    Measured: During the first 28 days of life (0-27days)

  6. Neonatal birthweight below the 3rd,5th and 10th centile.

    Birthweight and birthweight percentile for gestational age at delivery is calculated using a normal range derived in a Chinese population.

    Measured: At delivery

  7. Stillbirth or neonatal death

    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.

    Measured: At delivery

  8. <34 weeks and <37 weeks spontaneous preterm 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).

    Measured: At spontaneous delivery

  9. Gestational age

    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.

    Measured: At delivery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Oct 2022
  2. Study start3 Jul 2023
  3. Primary completion1 Jan 2025 (estimated)
  4. Study completion30 Nov 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
3,000 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05580523
Sponsor's protocol ID
MOST-AVERT
Status last verified
Nov 2023
First submitted
12 Oct 2022
Last updated
8 Nov 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Women's Heart Health Group of Chinese Society of Cardiology of Chinese Medical Association; Hypertension Group of Chinese Society of Cardiology of Chinese Medical Association. [Expert consensus on blood pressure management in hypertensive disorders of pregnancy (2019)]. Zhonghua Xin Xue Guan Bing Za Zhi. 2020 Mar 24;48(3):195-204. doi: 10.3760/cma.j.cn112148-20191024-00652. Chinese.

    PubMed 32234176
  • Witlin AG, Saade GR, Mattar F, Sibai BM. Predictors of neonatal outcome in women with severe preeclampsia or eclampsia between 24 and 33 weeks' gestation. Am J Obstet Gynecol. 2000 Mar;182(3):607-11. doi: 10.1067/mob.2000.104224.

    PubMed 10739516
  • Irgens HU, Reisaeter L, Irgens LM, Lie RT. Long term mortality of mothers and fathers after pre-eclampsia: population based cohort study. BMJ. 2001 Nov 24;323(7323):1213-7. doi: 10.1136/bmj.323.7323.1213.

    PubMed 11719411
  • von Dadelszen P, Magee LA, Roberts JM. Subclassification of preeclampsia. Hypertens Pregnancy. 2003;22(2):143-8. doi: 10.1081/PRG-120021060.

    PubMed 12908998
  • Chaemsaithong P, Pooh RK, Zheng M, Ma R, Chaiyasit N, Tokunaka M, Shaw SW, Seshadri S, Choolani M, Wataganara T, Yeo GSH, Wright A, Leung WC, Sekizawa A, Hu Y, Naruse K, Saito S, Sahota D, Leung TY, Poon LC. Prospective evaluation of screening performance of first-trimester prediction models for preterm preeclampsia in an Asian population. Am J Obstet Gynecol. 2019 Dec;221(6):650.e1-650.e16. doi: 10.1016/j.ajog.2019.09.041. Epub 2019 Oct 4.

    PubMed 31589866
  • Akolekar R, Syngelaki A, Sarquis R, Zvanca M, Nicolaides KH. Prediction of early, intermediate and late pre-eclampsia from maternal factors, biophysical and biochemical markers at 11-13 weeks. Prenat Diagn. 2011 Jan;31(1):66-74. doi: 10.1002/pd.2660.

    PubMed 21210481
  • Askie LM, Duley L, Henderson-Smart DJ, Stewart LA; PARIS Collaborative Group. Antiplatelet agents for prevention of pre-eclampsia: a meta-analysis of individual patient data. Lancet. 2007 May 26;369(9575):1791-1798. doi: 10.1016/S0140-6736(07)60712-0.

    PubMed 17512048
  • Rolnik DL, Wright D, Poon LC, O'Gorman N, Syngelaki A, de Paco Matallana C, Akolekar R, Cicero S, Janga D, Singh M, Molina FS, Persico N, Jani JC, Plasencia W, Papaioannou G, Tenenbaum-Gavish K, Meiri H, Gizurarson S, Maclagan K, Nicolaides KH. Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia. N Engl J Med. 2017 Aug 17;377(7):613-622. doi: 10.1056/NEJMoa1704559. Epub 2017 Jun 28.

    PubMed 28657417
  • Bujold E, Roberge S, Lacasse Y, Bureau M, Audibert F, Marcoux S, Forest JC, Giguere Y. Prevention of preeclampsia and intrauterine growth restriction with aspirin started in early pregnancy: a meta-analysis. Obstet Gynecol. 2010 Aug;116(2 Pt 1):402-414. doi: 10.1097/AOG.0b013e3181e9322a.

    PubMed 20664402
  • Roberge S, Villa P, Nicolaides K, Giguere Y, Vainio M, Bakthi A, Ebrashy A, Bujold E. Early administration of low-dose aspirin for the prevention of preterm and term preeclampsia: a systematic review and meta-analysis. Fetal Diagn Ther. 2012;31(3):141-6. doi: 10.1159/000336662. Epub 2012 Mar 21.

    PubMed 22441437
  • Roberge S, Nicolaides K, Demers S, Hyett J, Chaillet N, Bujold E. The role of aspirin dose on the prevention of preeclampsia and fetal growth restriction: systematic review and meta-analysis. Am J Obstet Gynecol. 2017 Feb;216(2):110-120.e6. doi: 10.1016/j.ajog.2016.09.076. Epub 2016 Sep 15.

    PubMed 27640943
  • Caron N, Rivard GE, Michon N, Morin F, Pilon D, Moutquin JM, Rey E. Low-dose ASA response using the PFA-100 in women with high-risk pregnancy. J Obstet Gynaecol Can. 2009 Nov;31(11):1022-1027. doi: 10.1016/S1701-2163(16)34346-8.

    PubMed 20175340
  • Rey E, Rivard GE. Is testing for aspirin response worthwhile in high-risk pregnancy? Eur J Obstet Gynecol Reprod Biol. 2011 Jul;157(1):38-42. doi: 10.1016/j.ejogrb.2011.02.026. Epub 2011 Mar 25.

    PubMed 21440360
  • Hypertensive Disorders in Pregnancy Subgroup, Chinese Society of Obstetrics and Gynecology, Chinese Medical Association. [Diagnosis and treatment of hypertension and pre-eclampsia in pregnancy: a clinical practice guideline in China(2020)]. Zhonghua Fu Chan Ke Za Zhi. 2020 Apr 25;55(4):227-238. doi: 10.3760/cma.j.cn112141-20200114-00039. Chinese.

    PubMed 32375429
  • Brownfoot FC, Hastie R, Hannan NJ, Cannon P, Tuohey L, Parry LJ, Senadheera S, Illanes SE, Kaitu'u-Lino TJ, Tong S. Metformin as a prevention and treatment for preeclampsia: effects on soluble fms-like tyrosine kinase 1 and soluble endoglin secretion and endothelial dysfunction. Am J Obstet Gynecol. 2016 Mar;214(3):356.e1-356.e15. doi: 10.1016/j.ajog.2015.12.019. Epub 2015 Dec 22.

    PubMed 26721779

Questions about this trial

What is this clinical trial studying?

A study testing 75 mg acetylsalicylic acid, 1.5g Metformin and 150 mg acetylsalicylic acid in people with Preeclampsia, run by Chinese University of Hong Kong at 6 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 8 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Chiu Yee, Liona Poon, MD ((852) 3505 1290, liona.poon@cuhk.edu.hk), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of preterm preeclampsia(<37 weeks) (time frame: ≥20 weeks to <37 weeks of gestation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05580523, which also lists 21 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2023.

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