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

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ClinicalTrials.gov Identifier: NCT03815110
Recruitment Status : Recruiting
First Posted : January 24, 2019
Last Update Posted : July 30, 2019
Sponsor:
Collaborator:
ThermoFisher Scientific Brahms Biomarkers France
Information provided by (Responsible Party):
Ravi Thadhani, 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.


Condition or disease
Preeclampsia and Eclampsia Preeclampsia Severe Gestational Hypertension Chronic Hypertension in Obstetric Context Superimposed Pre-Eclampsia Preeclampsia Mild

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.


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Study Type : Observational
Estimated Enrollment : 1000 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
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : May 2021

Resource links provided by the National Library of Medicine





Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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
Serum Sample (10 mL) Plasma Sample (10 mL) Urine Collection Saliva Swab


Information from the National Library of Medicine

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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
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.
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.

Information from the National Library of Medicine

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


Contacts
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Contact: Study Coordinator 310-423-0937 elizabeth.lemoine@cshs.org

Locations
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United States, California
Cedars-Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048
Contact: Study Coordinator    310-423-0937    elizabeth.lemoine@cshs.org   
UC San Francisco Medical Center Not yet recruiting
San Francisco, California, United States, 94158
Contact: Natalie Oman, MPH    415-502-0131      
United States, Illinois
University of Chicago Medical Center Recruiting
Chicago, Illinois, United States, 60637
Contact: Sarosh Rana, MD, MPH    773-562-4176    srana@bsd.uchicago.edu   
United States, Massachusetts
Tufts Medical Center Active, not recruiting
Boston, Massachusetts, United States, 02111
University of Massachusetts Memorial Medical Center Active, not recruiting
Worcester, Massachusetts, United States, 01605
United States, North Carolina
University of North Carolina Medical Center- Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599-7516
Contact: Karen Dorman, RN, MS    984-974-9012    kdorman@med.unc.edu   
United States, Pennsylvania
Lehigh Valley Health Network Active, not recruiting
Allentown, Pennsylvania, United States, 18102
United States, Texas
Baylor College of Medicine Active, not recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Cedars-Sinai Medical Center
ThermoFisher Scientific Brahms Biomarkers France
Investigators
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Principal Investigator: Ravi Thadhani, MD, MPH Cedars-Sinai Medical Center

Publications:

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Responsible Party: Ravi Thadhani, Vice Dean of Research and Education, Cedars-Sinai Medical Center
ClinicalTrials.gov Identifier: NCT03815110     History of Changes
Other Study ID Numbers: Pro00055135
First Posted: January 24, 2019    Key Record Dates
Last Update Posted: July 30, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Pre-Eclampsia
Eclampsia
Hypertension, Pregnancy-Induced
Hypertension
Vascular Diseases
Cardiovascular Diseases
Pregnancy Complications