- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02189148
First-trimester Prediction of Preeclampsia (PREDICTION)
First-trimester Prediction of Preeclampsia and Other Placenta-mediated Pregnancy Complications
Study Overview
Status
Detailed Description
Background: Preeclampsia (PE) is a placenta-mediated pregnancy complication related to adverse maternal and neonatal outcomes, including intra-uterine growth restriction (IUGR) and perinatal death. A growing body of evidence suggests that the preterm and severe forms of PE are associated with deep placentation disorders that occur early in gestation. Over the last decade, maternal characteristic and first-trimester biomarkers, including some that are already used for aneuploidy screening (PAPP-A) have been strongly related to the preterm and early forms of PE, suggesting that early prediction is possible. Preventive measures are actually recommended (low-dose aspirin; calcium) or under investigation (folic acid; low-molecular weight heparin; anti-oxidant) in high-risk women. However, only women with chronic disease or prior adverse pregnancy outcomes are eligible for these measures while most cases of PE occur in nulliparous women. Moreover, there are actually no clear guidelines for clinicians in Canada whose pregnant patients have one or several risk factors for preeclampsia (obesity, chronic hypertension, low PAPP-A, etc.). On the other hand, it has been suggested that prediction of PE, and particularly the most severe cases, is possible with high sensitivity and specificity by using a combination of anamnestic, biophysical, biochemical and ultrasonographic biomarkers using the web-based Fetal-Medicine Foundation (FMF) screening test. This suggests that a strategy of prediction and prevention of PE and other placenta-mediated complications is becoming possible for nulliparous women as well. However, certain major concerns must be addressed: 1) The FMF screening test has not been validated prospectively; 2) a controversy exists about the need and feasibility of Doppler ultrasound in the general population.
Objectives:
- To validate the 11-13 week FMF screening test for early-onset PE and a composite of placenta-mediated outcomes (preterm PE, IUGR <3rd percentile, stillbirth); and
- To compare the screening test with and without uterine artery (UtA) Doppler;
- To explore the efficiency of new potential biomarkers (ADAM-12; Placental protein (PP) -13; placental and subplacental volume; placental vascularization) for prediction of PE in our population.
Methods: A multicenter prospective observational study of nulliparous women recruited between 11 3/7 - 13 6/7 weeks (maternal characteristics; BMI; Mean arterial pressure (MAP); PAPP-A; placental growth factor (PIGF); UtA Doppler…) and followed until delivery. Delivery and neonatal data will be collected through chart reviews. Detection rates for early-onset PE (primary outcome) and other adverse pregnancy outcomes will be measured using the 11-13 weeks FMF screening test with and without UtA Doppler results. A case-cohort study will be performed using stored serum samples and three-dimensional ultrasound volume acquired at the 11-13 weeks visit.
Feasibility and power calculation: We estimate a minimum incidence of early-onset PE of 0.7%. A minimum of 7,600 women will be necessary to demonstrate that the FMF screening test is at least 80% sensitive and 90% specific where it is expected that it will be 95% sensitive and 92% specific. We will have the power to detect an absolute difference of 15% in the detection rate between the different screening strategies (± Doppler). Recruitment will take 3.0 years. The overall study will take 5.0 years.
Expectations: First, our research will potentially provide a validated, highly sensitive and specific, and cheap tool to help clinicians' decision in the care of nulliparous women with risk factors for PE. In case of negative results, the clinician will have good evidence to reassure the patients facing abnormal maternal serum screening values. The validation of a first-trimester screening strategy will strengthen clinical research on PE providing new information on the natural evolution of the disease. Finally, this study will contribute to develop the optimal design for randomized trials aiming at the prevention of early-onset PE and other placenta-mediated complications of pregnancy.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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Alberta
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Calgary, Alberta, Canada
- South Alberta Maternal Fetal Medicine Centre, University of Calgary
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Ontario
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Toronto, Ontario, Canada, M5G 1X5
- Sinai Health System, Mount Sinai Hospital
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Quebec
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Montreal, Quebec, Canada, H3T 1C5
- CHU Ste-Justine
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Quebec city, Quebec, Canada, G1V 4G2
- CHU de Québec
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Nulliparous women who will deliver in one of the participating center:
CHUL Hospital, Quebec city, QC Hôpital Saint-François-d'Assise, Quebec city, QC CHU Ste-Justine, Montreal, QC Southern Alberta Maternal Fetal Medicine Centre, Calgary, Alberta Sinai Health System, Mount Sinai Hospital, Toronto, Ontario
Description
Inclusion Criteria:
- gestational age between 11 3/7 and 13 6/7 weeks;
- nulliparous women (no previous delivery ≥ 20 weeks).
Exclusion Criteria:
- pregnant women <18 years old at recruitment;
- multiple pregnancies;
- fetal congenital malformation;
- positive for HIV or hepatitis C or hepatitis B;
- negative fetal heart at recruitment;
- women planning a delivery outside the participating hospitals;
- women not able to provide an informed consent to the study.
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
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Cohort
Each participant will :
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
early onset preeclampsia
Time Frame: diagnosed between 20 and 34 weeks of gestation
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Preeclampsia will be defined according to the Canadian Guidelines for Diagnosis, Evaluation, and Management of the Hypertensive Disorders of Pregnancy guidelines, as de novo hypertension with diastolic blood pressure >90 mmHg on two occasions at least four hours apart, after 20 weeks of pregnancy, associated with proteinuria ≥300 mg/24 h or at least '2 +' protein on urine dipstick or an adverse conditions
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diagnosed between 20 and 34 weeks of gestation
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Severe preeclampsia
Time Frame: between 20 and 42 weeks of gestation
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Severe Preeclampsia will be defined by the presence of at least one of the following adverse condition: 1) systolic blood pressure ≥ 160 mmHg and diastolic blood pressure ≥ 110 mmHg after 4 h of bed rest, 2) proteinuria ≥ 5 g/24 h or at least '3 +' protein on urine dipstick, or 3) oliguria < 400 ml/24 h; 4) cerebral or visual disturbances; epigastric pain; pulmonary edema or cyanosis; thrombocytopenia <100,000mm
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between 20 and 42 weeks of gestation
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Fetal growth restriction
Time Frame: between 20 and 42 weeks of gestation
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Fetal growth restriction will be defined as a birth weight below the 10th centile (or below the 3rd centile for severe FGR) of Canadian reference growth charts.
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between 20 and 42 weeks of gestation
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: François Audibert, MD, MSc, St. Justine's Hospital
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CIHR-MOP-133672
- B14-05-2024 (OTHER: CER-CHU de Quebec)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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