Prevention of Pre-eclampsia Using Metformin: a Randomized Control Trial

Summary

This is an open label, randomized control trial (RCT) in which high risk for pre-eclampsia pregnant subjects will be randomly assigned to either an intervention group (metformin 1 gm twice daily plus aspirin 100 mg per day and standard of care) versus control group (aspirin 100 mg per day and standard of care) that will be administered between 11 to 13 weeks of gestation until delivery . Only women at high risk of pre-eclampsia as defined by the ACOG practice bulletin will be included (see inclusion criteria). Patient assignment will not be blinded as control group will not be given a placebo; the data will be analyzed on an intention to treat basis. Enrolled subjects will be followed throughout pregnancy and up to 30 days post-delivery (as per hospital practice).

Timeline

Start

2022-03-24

Primary completion

2023-04-24

Completion

2023-12-30

Publications

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• Background Levine RJ, Maynard SE, Qian C, Lim KH, England LJ, Yu KF, Schisterman EF, Thadhani R, Sachs BP, Epstein FH, Sibai BM, Sukhatme VP, Karumanchi SA. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004 Feb 12;350(7):672-83. doi: 10.1056/NEJMoa031884. Epub 2004 Feb 5.
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• Background Yusuf AM, Kahane A, Ray JG. First and Second Trimester Serum sFlt-1/PlGF Ratio and Subsequent Preeclampsia: A Systematic Review. J Obstet Gynaecol Can. 2018 May;40(5):618-626. doi: 10.1016/j.jogc.2017.07.014. Epub 2017 Sep 15.
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• Background Zhao M, Zhu Z, Liu C, Zhang Z. Dual-cutoff of sFlt-1/PlGF ratio in the stratification of preeclampsia: a systematic review and meta-analysis. Arch Gynecol Obstet. 2017 May;295(5):1079-1087. doi: 10.1007/s00404-017-4302-3. Epub 2017 Mar 17.
• Background Stepan H, Herraiz I, Schlembach D, Verlohren S, Brennecke S, Chantraine F, Klein E, Lapaire O, Llurba E, Ramoni A, Vatish M, Wertaschnigg D, Galindo A. Implementation of the sFlt-1/PlGF ratio for prediction and diagnosis of pre-eclampsia in singleton pregnancy: implications for clinical practice. Ultrasound Obstet Gynecol. 2015 Mar;45(3):241-6. doi: 10.1002/uog.14799. No abstract available.
• Background Syngelaki A, Nicolaides KH, Balani J, Hyer S, Akolekar R, Kotecha R, Pastides A, Shehata H. Metformin versus Placebo in Obese Pregnant Women without Diabetes Mellitus. N Engl J Med. 2016 Feb 4;374(5):434-43. doi: 10.1056/NEJMoa1509819.
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• Background Zheng J, Shan PF, Gu W. The efficacy of metformin in pregnant women with polycystic ovary syndrome: a meta-analysis of clinical trials. J Endocrinol Invest. 2013 Nov;36(10):797-802. doi: 10.3275/8932. Epub 2013 Apr 12.
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• Background Zhu B, Zhang L, Fan YY, Wang L, Li XG, Liu T, Cao YS, Zhao ZG. Metformin versus insulin in gestational diabetes mellitus: a meta-analysis of randomized clinical trials. Ir J Med Sci. 2016 May;185(2):371-81. doi: 10.1007/s11845-016-1414-x. Epub 2016 Feb 9.
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• Background Chasan-Taber L, Silveira M, Waring ME, Pekow P, Braun B, Manson JE, Solomon CG, Markenson G. Gestational Weight Gain, Body Mass Index, and Risk of Hypertensive Disorders of Pregnancy in a Predominantly Puerto Rican Population. Matern Child Health J. 2016 Sep;20(9):1804-13. doi: 10.1007/s10995-016-1983-3.
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