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

NCT ID: NCT03815110

Last Updated: 2022-11-28

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 1050 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-12-20
• Study Completion Date: 2022-10-01

Brief Summary

The purpose of this study is to

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.

And

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.

Subjects will provide blood, urine, and saliva samples at the time of enrollment. Samples will be frozen for batch assessment of sFLT-1 and PlGF levels by automated assays. Clinicians, subjects, and researchers will be blinded to protein level assessment, therefore assay results will not affect clinical management.

Detailed Description

Preeclampsia is a leading cause of maternal and fetal morbidity and mortality in the US, and affects about 5% of pregnancies. Despite its morbidity, preeclampsia is challenging to distinguish from worsening chronic hypertension or gestational hypertension. Furthermore, it is challenging to identify who among those with hypertensive disorders of pregnancy will develop preeclampsia with severe features, including kidney, liver, pulmonary, or cerebral injury. The only definitive treatment is delivery of the placenta, and therefore the fetus, which can lead to severe morbidity and mortality to the neonate if delivery is very premature. New methods of risk stratification are needed to identify who among women with hypertensive disorders of pregnancy are at risk of developing preeclampsia with severe features in order to allocate resources (e.g. betamethasone and magnesium for fetal neuroprotection) accordingly.

Several serum proteins (sFLT-1 and PlGF) correlate well with the development of preeclampsia, particularly with preeclampsia with severe features, and may be used to predict the development of preeclampsia with severe features within a certain timeframe. The goal of this study is to identify a cut-off of the sFLT-1/PlGF ratio using automated assays that differentiates women who will develop preeclampsia with severe features from those who will not among women with hypertensive disorders of pregnancy within 2 weeks of testing. The secondary outcomes include time to delivery, the performance of the cut-off to predict adverse maternal and adverse fetal outcomes, and a comparison of the performance of the cut-off with clinical and laboratory factors per American College of Obstetricians and Gynecologists (ACOG) guidelines. Investigators will also look at the levels of sFLT-1 and PlGF in the urine and the saliva to determine if they correlate well with serum levels and may provide a less invasive alternative to serum samples.

Conditions

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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 1. 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

ThermoFisher Scientific Brahms Biomarkers France

INDUSTRY

Sponsor Role: collaborator

Cedars-Sinai Medical Center

OTHER

Sponsor Role: lead

Responsible Party

S Ananth Karumanchi

Lead Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ananth Karumanchi, MD

Role: PRINCIPAL_INVESTIGATOR

Cedars-Sinai Medical Center

Locations

Cedars-Sinai Medical Center

Los Angeles, California, United States

Sharp Mary Birch Hospital for Women & Newborns

San Diego, California, United States

UC San Francisco Medical Center

San Francisco, California, United States

Torrance Memorial Medical Center

Torrance, California, United States

University of South Florida

Tampa, Florida, United States

University of Chicago Medical Center

Chicago, Illinois, United States

Northshore

Evanston, Illinois, United States

MedStar Health

Baltimore, Maryland, United States

Johns Hopkins University Medical Center

Baltimore, Maryland, United States

Tufts Medical Center

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, United States

University of North Carolina Medical Center- Chapel Hill

Chapel Hill, North Carolina, United States

Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Miami Valley Hospital

Dayton, Ohio, United States

Lehigh Valley Health Network

Allentown, Pennsylvania, United States

Baylor College of Medicine

Houston, Texas, United States

University of Utah

Salt Lake City, Utah, United States

Countries

United States

References

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Reference Type: BACKGROUND

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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.

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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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.

Reference Type: DERIVED

PMID: 38319832 (View on PubMed)

Other Identifiers

Pro00055135

Identifier Type: -

Identifier Source: org_study_id