Preeclampsia Risk Assessment: Evaluation of Cut-offs to Improve Stratification

NCT03815110 | Completed

• 1 other identifier: Pro00055135
• Study Type: observational
• Target: 1,050
• Locations: 1 country
• Sites: 18

Brief Summary

The purpose of this study is to

1. 1.Identify a cut-off for the ratio of the serum proteins soluble FMS-like Tyrosine Kinase 1 (sFLT-1) and placental growth factor (PlGF) that identifies women will who develop preeclampsia with severe features within 2 weeks of testing (clinically positive) from those who do not develop preeclampsia with severe features within 2 weeks of testing (clinically negative) among preterm pregnant women with hypertensive disorders of pregnancy.
2. 2.To validate the cut-off the ratio of sFLT-1 and PlGF and to validate the performance of the automated assays used to find the cut-off. Test performance includes positive predictive value, negative predictive value, sensitivity, and specificity.

Conditions

Preeclampsia and Eclampsia; Preeclampsia Severe; Gestational Hypertension; Chronic Hypertension in Obstetric Context; Superimposed Pre-Eclampsia; Preeclampsia Mild

Outcome Measures

Primary Outcomes (2)

• Derivation and Performance of Cut-off for sFLT-1/PlGF Ratio (Serum)

  Identification of the cut-off and performance (sensitivity, specificity, positive predictive value, and negative predictive value) for the sFLT-1/PlGF ratio as determined by automated assays that enable differentiation of those women with a hypertensive disorder of pregnancy who develop preeclampsia with severe features from those who do not develop preeclampsia within 2 weeks of testing.

  2 weeks

• Validation of Cut-off and Performance of sFLT-1/PlGF Ratio as Defined in Derivation Cohort (Serum)

  Validation of the performance (sensitivity, specificity, positive predictive value, negative predictive value) of the cut-off of the sFLT-1/PlGF ratio differentiating the development of preeclampsia with severe features within 2 weeks after testing as determined by the independent Derivation cohort.

  2 weeks

Secondary Outcomes (6)

• Performance in Determining the Risk for Adverse Maternal Outcomes

  2 weeks

• Performance in Determining the Risk for Adverse Fetal/Neonatal Outcomes

  4 weeks

• Performance As Compared to ACOG-Guidelines

  2 years

• Performance of sFLT-1/PlGF & ACOG Guidelines

  2 years

• Time to Delivery

  2 years

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population includes women with singleton pregnancies at 23+0 to 34+6/7 weeks gestational age who are hospitalized with (or develop while hospitalized) a hypertensive disorder of pregnancy. Minors and patients who have received intravenous heparin within 24 hours of enrollment or who have participated in a therapeutic interventional study in the last 30 days will be excluded.

You may qualify if:

• Signed informed consent in a pregnant woman ≥ 18 years of age.
• Gestational age 23+0 to 34+6/7 weeks
• Singleton pregnancy
• Hospitalized with (or develop while hospitalized) a hypertensive disorder of pregnancy (preeclampsia, chronic hypertension with or without superimposed preeclampsia or gestational hypertension) as defined by ACOG guidelines.

You may not qualify if:

• \. Patients who have received intravenous heparin within 24 hours of enrollment. Low dose subcutaneous heparin or low molecular weight heparin (LMWH) for prophylaxis of deep venous thrombosis (DVT) is permitted.
• Patients who are currently participating in another clinical trial to evaluate a new therapeutic intervention or who have participated in another such trial in the previous 30 days.
• Multiple gestations.

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead
• ThermoFisher Scientific Brahms Biomarkers France: collaborator

Study Sites (18)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Sharp Mary Birch Hospital for Women & Newborns

San Diego, California, 92123, United States

Location

UC San Francisco Medical Center

San Francisco, California, 94158, United States

Location

Torrance Memorial Medical Center

Torrance, California, 90505, United States

Location

University of South Florida

Tampa, Florida, 33606, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Northshore

Evanston, Illinois, 60201, United States

Location

MedStar Health

Baltimore, Maryland, 21237, United States

Location

Johns Hopkins University Medical Center

Baltimore, Maryland, 21287, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, 01605, United States

Location

University of North Carolina Medical Center- Chapel Hill

Chapel Hill, North Carolina, 27599-7516, United States

Location

Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Miami Valley Hospital

Dayton, Ohio, 45409, United States

Location

Lehigh Valley Health Network

Allentown, Pennsylvania, 18102, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Related Publications (8)

• Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013 Nov;122(5):1122-1131. doi: 10.1097/01.AOG.0000437382.03963.88. No abstract available.

  PMID: 24150027 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.

  PMID: 14764923 BACKGROUND

• Sunderji S, Gaziano E, Wothe D, Rogers LC, Sibai B, Karumanchi SA, Hodges-Savola C. Automated assays for sVEGF R1 and PlGF as an aid in the diagnosis of preterm preeclampsia: a prospective clinical study. Am J Obstet Gynecol. 2010 Jan;202(1):40.e1-7. doi: 10.1016/j.ajog.2009.07.025. Epub 2009 Sep 17.

  PMID: 19762001 BACKGROUND

• Engels T, Pape J, Schoofs K, Henrich W, Verlohren S. Automated measurement of sFlt1, PlGF and sFlt1/PlGF ratio in differential diagnosis of hypertensive pregnancy disorders. Hypertens Pregnancy. 2013 Nov;32(4):459-73. doi: 10.3109/10641955.2013.827205. Epub 2013 Aug 19.

  PMID: 23957293 BACKGROUND

• Verlohren S, Herraiz I, Lapaire O, Schlembach D, Moertl M, Zeisler H, Calda P, Holzgreve W, Galindo A, Engels T, Denk B, Stepan H. The sFlt-1/PlGF ratio in different types of hypertensive pregnancy disorders and its prognostic potential in preeclamptic patients. Am J Obstet Gynecol. 2012 Jan;206(1):58.e1-8. doi: 10.1016/j.ajog.2011.07.037. Epub 2011 Jul 30.

  PMID: 22000672 BACKGROUND

• Rana S, Powe CE, Salahuddin S, Verlohren S, Perschel FH, Levine RJ, Lim KH, Wenger JB, Thadhani R, Karumanchi SA. Angiogenic factors and the risk of adverse outcomes in women with suspected preeclampsia. Circulation. 2012 Feb 21;125(7):911-9. doi: 10.1161/CIRCULATIONAHA.111.054361. Epub 2012 Jan 18.

  PMID: 22261192 BACKGROUND

• Zeisler H, Llurba E, Chantraine F, Vatish M, Staff AC, Sennstrom M, Olovsson M, Brennecke SP, Stepan H, Allegranza D, Dilba P, Schoedl M, Hund M, Verlohren S. Predictive Value of the sFlt-1:PlGF Ratio in Women with Suspected Preeclampsia. N Engl J Med. 2016 Jan 7;374(1):13-22. doi: 10.1056/NEJMoa1414838.

  PMID: 26735990 BACKGROUND

• Thadhani R, Lemoine E, Rana S, Costantine MM, Calsavara VF, Boggess K, Wylie BJ, Moore Simas TA, Louis JM, Espinoza J, Gaw SL, Murtha A, Wiegand S, Gollin Y, Singh D, Silver RM, Durie DE, Panda B, Norwitz ER, Burd I, Plunkett B, Scott RK, Gaden A, Bautista M, Chang Y, Diniz MA, Karumanchi SA, Kilpatrick S. Circulating Angiogenic Factor Levels in Hypertensive Disorders of Pregnancy. NEJM Evid. 2022 Dec;1(12):EVIDoa2200161. doi: 10.1056/EVIDoa2200161. Epub 2022 Nov 9.

  PMID: 38319832 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Serum Sample (10 mL) Plasma Sample (10 mL) Urine Collection Saliva Swab

MeSH Terms

Conditions

Pre-Eclampsia; Eclampsia; Hypertension, Pregnancy-Induced

Condition Hierarchy (Ancestors)

Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Ananth Karumanchi, MD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lead Principal Investigator

Study Record Dates

• First Submitted: January 17, 2019
• First Posted: January 24, 2019
• Study Start: December 20, 2018
• Primary Completion: November 19, 2021
• Study Completion: October 1, 2022
• Last Updated: November 28, 2022

Record last verified: 2022-11

Locations

US (18)