Preeclampsia Risk Assessment: Evaluation of Cut-offs to Improve Stratification (PRAECIS)
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| ClinicalTrials.gov Identifier: NCT03815110 |
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Recruitment Status :
Completed
First Posted : January 24, 2019
Last Update Posted : November 28, 2022
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The purpose of this study is to
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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
- 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.
| Condition or disease |
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| Preeclampsia and Eclampsia Preeclampsia Severe Gestational Hypertension Chronic Hypertension in Obstetric Context Superimposed Pre-Eclampsia Preeclampsia Mild |
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.
| Study Type : | Observational |
| Actual Enrollment : | 1050 participants |
| Observational Model: | Cohort |
| Time Perspective: | Prospective |
| Official Title: | Preeclampsia Risk Assessment: Evaluation of Cut-offs to Improve Stratification |
| Actual Study Start Date : | December 20, 2018 |
| Actual Primary Completion Date : | November 19, 2021 |
| Actual Study Completion Date : | October 1, 2022 |
- Derivation and Performance of Cut-off for sFLT-1/PlGF Ratio (Serum) [ Time Frame: 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.
- Validation of Cut-off and Performance of sFLT-1/PlGF Ratio as Defined in Derivation Cohort (Serum) [ Time Frame: 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.
- Performance in Determining the Risk for Adverse Maternal Outcomes [ Time Frame: 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 in Determining the Risk for Adverse Fetal/Neonatal Outcomes [ Time Frame: 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 [ Time Frame: 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/dL
- Performance of sFLT-1/PlGF & ACOG Guidelines [ Time Frame: 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/dL
- Time to Delivery [ Time Frame: 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.
- sFLT-1 and PlGF Levels in Urine and Saliva [ Time Frame: 2 years ]Identification of levels of sFLT-1 (pg/ml) and PlGF (pg/ml) in urine and saliva specimens.
Biospecimen Retention: Samples With DNA
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
| Sampling Method: | Non-Probability Sample |
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03815110
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| Principal Investigator: | Ananth Karumanchi, MD | Cedars-Sinai Medical Center |
| Responsible Party: | S Ananth Karumanchi, Lead Principal Investigator, Cedars-Sinai Medical Center |
| ClinicalTrials.gov Identifier: | NCT03815110 |
| Other Study ID Numbers: |
Pro00055135 |
| First Posted: | January 24, 2019 Key Record Dates |
| Last Update Posted: | November 28, 2022 |
| Last Verified: | November 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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Pre-Eclampsia Eclampsia Hypertension, Pregnancy-Induced Hypertension Vascular Diseases |
Cardiovascular Diseases Pregnancy Complications Female Urogenital Diseases and Pregnancy Complications Urogenital Diseases |