Preeclampsia Risk Assessment: Evaluation of Cut-offs to Improve Stratification
- Conditions
- Preeclampsia and EclampsiaGestational HypertensionPreeclampsia MildPreeclampsia SevereChronic Hypertension in Obstetric ContextSuperimposed Pre-Eclampsia
- Registration Number
- NCT03815110
- Lead Sponsor
- Cedars-Sinai Medical Center
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 1050
- 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.
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- 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.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Validation of Cut-off and Performance of sFLT-1/PlGF Ratio as Defined in Derivation Cohort (Serum) 2 weeks 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.
Derivation and Performance of Cut-off for sFLT-1/PlGF Ratio (Serum) 2 weeks 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.
- Secondary Outcome Measures
Name Time Method Performance in Determining the Risk for Adverse Maternal Outcomes 2 weeks Performance (sensitivity, specificity, positive predictive value, negative predictive value) of the sFLT-1/PlGF cut-off identified and validated per primary endpoint in determining the risk of adverse maternal outcomes within 2 weeks after testing.
Performance of sFLT-1/PlGF & ACOG Guidelines 2 years Performance of the algorithm combining the sFLT-1/PlGF ratio PLUS clinical and laboratory factors per ACOG guidelines in predicting maternal development of preeclampsia with severe features.
ACOG guidelines in predicting the development of preeclampsia include,
* systolic blood pressure of 140 mm Hg or more or diastolic blood pressure of 90 mm HG or more on at least 2 occasions at least 4 hours apart
* 300 mg or more of protein per 24 hour urine collection
* Protein/creatinine ration of 0.3 mg/dL or more
* Urine dipstick reading of 2+
* Uric acid greater than 5 mg/dLPerformance in Determining the Risk for Adverse Fetal/Neonatal Outcomes 4 weeks Performance (sensitivity, specificity, positive predictive value, negative predictive value) of the sFLT-1/PlGF cut-off identified and validated per primary endpoint in determining the risk of adverse fetal/neonatal outcomes within 2 weeks after testing.
Performance As Compared to ACOG-Guidelines 2 years Performance of the sFLT-1/PlGF ratio versus the performance of clinical and laboratory factors per ACOG guidelines in predicting maternal development of preeclampsia with severe features.
ACOG guidelines in predicting the development of preeclampsia include,
* systolic blood pressure of 140 mm Hg or more or diastolic blood pressure of 90 mm HG or more on at least 2 occasions at least 4 hours apart
* 300 mg or more of protein per 24 hour urine collection
* Protein/creatinine ration of 0.3 mg/dL or more
* Urine dipstick reading of 2+
* Uric acid greater than 5 mg/dLsFLT-1 and PlGF Levels in Urine and Saliva 2 years Identification of levels of sFLT-1 (pg/ml) and PlGF (pg/ml) in urine and saliva specimens.
Time to Delivery 2 years Time to delivery in women whose sFLT-1/PlGF ratio is above the cut-off as identified per the primary objective compared to those whose sFLT-1/PlGF ratio is below that cut-off.
Trial Locations
- Locations (18)
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
UC San Francisco Medical Center
🇺🇸San Francisco, California, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
MedStar Health
🇺🇸Baltimore, Maryland, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
University of Massachusetts Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
Torrance Memorial Medical Center
🇺🇸Torrance, California, United States
Northshore
🇺🇸Evanston, Illinois, United States
Johns Hopkins University Medical Center
🇺🇸Baltimore, Maryland, United States
Sharp Mary Birch Hospital for Women & Newborns
🇺🇸San Diego, California, United States
Ohio State University Wexner Medical Center
🇺🇸Columbus, Ohio, United States
Lehigh Valley Health Network
🇺🇸Allentown, Pennsylvania, United States
Miami Valley Hospital
🇺🇸Dayton, Ohio, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
University of North Carolina Medical Center- Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
University of South Florida
🇺🇸Tampa, Florida, United States