Clinical trial NCT00763672: MorbiMortality Amelioration in Preeclamptic Primiparas Study. MoMA Pre Prim Study
Official title: Impact of a Single Second-trimester Plasma sFlt-1 and/or Urinary PlGF Assay on Maternofetal Morbidity/Mortality
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pregnancy
Primiparity
Hypertension
Preeclampsia
Intrauterine Growth Retardation
Keywords: Preeclampsia
Hypertension
Intra uterine growth retardation
Antiangiogenic factor
Prevention
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2008-10-01
Enrollment: 1040
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to determine whether close monitoring of patients with a high sFlt1 plasma level between 25 and 28 weeks of gestation (i.e. at high risk of subsequent preeclampsia) improves maternal and fetal outcomes. The investigator hypothesize that 1/ early screening for preeclampsia by plasmatic sFlt1 will reduce maternal and fetal mortality and morbidity and 2/ a simple urinary PlGF screening will be effective.

Detailed description: We will measure plasmatic sFlt-1 level between 25 and 28 weeks of gestation and flow velocity of uterine arteries by Doppler (22 - 26 weeks of gestation) in primipara. Patients will be stratified according to the results of the uterine artery Doppler measurement, and then randomized in two groups A and B. In group A, sFlt-1 concentration will be communicated to the obstetrician (+ or -): the threshold of abnormally high plasmatic concentration of sFlt-1 is 957 ng/mL. In patients with a high plasmatic concentration of sFlt-1 (+), the pregnancy will be closely monitored including repeated clinical, biological, and ultrasound examinations. Patients with sFlt-1 plasmatic concentration below 957 ng/mL (-) will be routinely followed-up.In group B, the result of sFlt-1 measurement will not be communicated and the pregnancy will be routinely monitored.Abnormal Doppler recordings in either group will result in a close monitoring as per our usual local practice. Urinary PlGF (expressed as a ratio PlGF/creatininemia) will also be measured and the results will be analyzed at the end of the study. Beside sFlt-1, we will store the plasmatic samples to measure other biomarkers that could be relevant in the future (no DNA analysis will be done without a new patient consent).

Eligibility criteria: Inclusion Criteria:

* Pregnant womenAge ≥ 18 years
* Followed in our center before the 28th week of gestation
* Under social security coverage
* Signed informed consent

Exclusion Criteria:

* Age \< 18 years
* Followed in our center after the 28th week of gestation
* No social security coverage
* Refusal to be included

Primary outcomes:
measure: Reduction in the maternal and fetal morbimortality score
timeFrame: During the pregnancy and the 3 first month of the child
Secondary outcomes:
measure: Child status
timeFrame: at 3 months post-delivery
measure: Length of hospital stay during pregnancy and post-partum periods
timeFrame: during pregnancy and post-partum periods
measure: Predictive value for vascula-renal disease of urinary PlGF as compared with plasmatic sFlt-1.
timeFrame: between 25 and 28 weeks of gestation
Other outcomes:
Locations:
city: Paris
country: France
facility: Department of Gynecology Obstetrics and Reproductive Medicine, Hôpital Tenon, AP-HP, UPMC
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Nadia BERKANE, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Nagamatsu T, Fujii T, Kusumi M, Zou L, Yamashita T, Osuga Y, Momoeda M, Kozuma S, Taketani Y. Cytotrophoblasts up-regulate soluble fms-like tyrosine kinase-1 expression under reduced oxygen: an implication for the placental vascular development and the pathophysiology of preeclampsia. Endocrinology. 2004 Nov;145(11):4838-45. doi: 10.1210/en.2004-0533. Epub 2004 Jul 29.
citation: Familoni OB, Adefuye PO, Olunuga TO. Pattern and factors affecting the outcome of pregnancy in hypertensive patients. J Natl Med Assoc. 2004 Dec;96(12):1626-31.
citation: Maynard SE, Min JY, Merchan J, Lim KH, Li J, Mondal S, Libermann TA, Morgan JP, Sellke FW, Stillman IE, Epstein FH, Sukhatme VP, Karumanchi SA. Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest. 2003 Mar;111(5):649-58. doi: 10.1172/JCI17189.
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citation: Luttun A, Carmeliet P. Soluble VEGF receptor Flt1: the elusive preeclampsia factor discovered? J Clin Invest. 2003 Mar;111(5):600-2. doi: 10.1172/JCI18015. No abstract available.
citation: Koga K, Osuga Y, Yoshino O, Hirota Y, Ruimeng X, Hirata T, Takeda S, Yano T, Tsutsumi O, Taketani Y. Elevated serum soluble vascular endothelial growth factor receptor 1 (sVEGFR-1) levels in women with preeclampsia. J Clin Endocrinol Metab. 2003 May;88(5):2348-51. doi: 10.1210/jc.2002-021942.
citation: Romero R, Nien JK, Espinoza J, Todem D, Fu W, Chung H, Kusanovic JP, Gotsch F, Erez O, Mazaki-Tovi S, Gomez R, Edwin S, Chaiworapongsa T, Levine RJ, Karumanchi SA. A longitudinal study of angiogenic (placental growth factor) and anti-angiogenic (soluble endoglin and soluble vascular endothelial growth factor receptor-1) factors in normal pregnancy and patients destined to develop preeclampsia and deliver a small for gestational age neonate. J Matern Fetal Neonatal Med. 2008 Jan;21(1):9-23. doi: 10.1080/14767050701830480.
citation: Stepan H, Geide A, Faber R. Soluble fms-like tyrosine kinase 1. N Engl J Med. 2004 Nov 18;351(21):2241-2. doi: 10.1056/NEJM200411183512123. No abstract available.
citation: 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.
citation: Hertig A, Berkane N, Lefevre G, Toumi K, Marti HP, Capeau J, Uzan S, Rondeau E. Maternal serum sFlt1 concentration is an early and reliable predictive marker of preeclampsia. Clin Chem. 2004 Sep;50(9):1702-3. doi: 10.1373/clinchem.2004.036715. No abstract available.
citation: Levine RJ, Thadhani R, Qian C, Lam C, Lim KH, Yu KF, Blink AL, Sachs BP, Epstein FH, Sibai BM, Sukhatme VP, Karumanchi SA. Urinary placental growth factor and risk of preeclampsia. JAMA. 2005 Jan 5;293(1):77-85. doi: 10.1001/jama.293.1.77.
citation: Berkane N, Hertig A, Rondeau E, Uzan S. Hypertensive disorders of pregnancy: future perspectives. A French point of view. Curr Opin Obstet Gynecol. 2008 Apr;20(2):107-9. doi: 10.1097/GCO.0b013e3282f73391. No abstract available.