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First-trimester Prediction of Preeclampsia (PREDICTION)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02189148
Recruitment Status : Completed
First Posted : July 14, 2014
Last Update Posted : July 23, 2019
Sponsor:
Collaborators:
Canadian Institutes of Health Research (CIHR)
Laval University
Information provided by (Responsible Party):
Emmanuel Bujold, CHU de Quebec-Universite Laval

Tracking Information
First Submitted Date July 10, 2014
First Posted Date July 14, 2014
Last Update Posted Date July 23, 2019
Study Start Date November 2014
Actual Primary Completion Date December 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: July 11, 2014)
early onset preeclampsia [ Time Frame: diagnosed between 20 and 34 weeks of gestation ]
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
Original Primary Outcome Measures Same as current
Change History Complete list of historical versions of study NCT02189148 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: July 11, 2014)
  • Severe preeclampsia [ Time Frame: between 20 and 42 weeks of gestation ]
    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
  • Fetal growth restriction [ Time Frame: between 20 and 42 weeks of gestation ]
    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.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title First-trimester Prediction of Preeclampsia
Official Title First-trimester Prediction of Preeclampsia and Other Placenta-mediated Pregnancy Complications
Brief Summary Preeclampsia is a complication of pregnancy related to adverse maternal and neonatal outcomes, including fetal growth restriction and perinatal death. Several measures are used or under investigation (low-dose aspirin, low-molecular weight heparin, calcium, folic acid, among others) for the prevention of preeclampsia. Unfortunately, most high-risk women who could benefit from those preventive measures are not identified until late in pregnancy. Recent evidences suggest that the investigators could identify women at risk of developing preeclampsia using a combination of serum and ultrasound biomarkers in the first-trimester of pregnancy. This screening test needs external validation. A first-trimester screening strategy will strengthen clinical research on preeclampsia and will contribute to the development of strategy combining the prediction and prevention of the disease and its related complications.
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:

  1. 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
  2. To compare the screening test with and without uterine artery (UtA) Doppler;
  3. 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 Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
Description:
Maternal serum
Sampling Method Non-Probability Sample
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

Condition
  • Preeclampsia
  • Severe Preeclampsia
  • Fetal Growth Restriction
  • Preterm Birth
Intervention Not Provided
Study Groups/Cohorts Cohort

Each participant will :

  • give consent
  • provide a blood sample (10 ml)
  • be measured (weight and height for BMI calculation)
  • undergo a blood pressure measurement
  • have an ultrasound exam (uterine arteries Doppler, placental volume, thickness of the placenta)
  • answer to a short questionnaire (5 pages)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: July 22, 2019)
7554
Original Estimated Enrollment
 (submitted: July 11, 2014)
7600
Actual Study Completion Date March 2018
Actual Primary Completion Date December 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria

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.
Sex/Gender
Sexes Eligible for Study: Female
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Canada
Removed Location Countries  
 
Administrative Information
NCT Number NCT02189148
Other Study ID Numbers CIHR-MOP-133672
B14-05-2024 ( Other Identifier: CER-CHU de Quebec )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Emmanuel Bujold, CHU de Quebec-Universite Laval
Study Sponsor CHU de Quebec-Universite Laval
Collaborators
  • Canadian Institutes of Health Research (CIHR)
  • Laval University
Investigators
Principal Investigator: Emmanuel Bujold, MD, MSc CHU de Québec
Principal Investigator: François Audibert, MD, MSc St. Justine's Hospital
PRS Account CHU de Quebec-Universite Laval
Verification Date July 2018