Predicting Late-onset Preeclampsia at 10-14 Weeks of Pregnancy

October 16, 2020 updated by: University of Southern Denmark

First Trimester Screening for Late-onset Preeclampsia: Evaluation of Novel Predictive Biomarker MMP-7 in Combination With MAP and Uterine Artery Pulsatility Index in a Danish Population

The aim of this study is to make it easier to predict late-onset preeclampsia at 11-14 weeks of pregnancy. This will be done by measuring certain proteins in the mother's blood together with obtaining the mother's medical history, ultrasound of the mother's blood supply to the uterus, and her blood pressure.

All expectant mothers who meet the inclusion criteria will be invited to participate in the study, and those that agree will have the above mentioned factors measured at their first trimester scan appointment. The data will be registered in an online database, and the blood samples will be saved in a biobank at the hospital.

When the women have then given birth around six months later, the data will be analyzed, and whether or not the individual woman ended up developing preeclampsia will be found out from her medical records. It will then be possible to see if blood samples, medical history, blood supply to the uterus, and/or blood pressure are connected to development of preeclampsia.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Detailed Description

The aim of this study is to improve the current first-trimester screening regimes for early detection of late-onset preeclampsia (PE) using maternal serum biomarkers in combination with maternal history, uterine artery flow, and mean arterial blood pressure.

Hypothesis: Matrix metalloproteinase 7 (MMP-7) in combination with maternal history, uterine artery flow and mean arterial blood pressure can improve the detection rate of late onset PE.

The Fetal Medicine Foundation (FMF) algorithm is developed with the objective of identifying women at high risk of PE in the first trimester of pregnancy, allowing for effective prophylactic use of low-dose acetylsalicylic acid (ASA) started before 16 weeks of pregnancy. The algorithm utilizes Bayes' theorem by combining maternal characteristics and medical history with uterine artery pulsatility index (PI), mean arterial pressure (MAP), maternal serum pregnancy-associated plasma protein-A (PAPP-A), and placental growth factor (PlGF) and has been validated in several populations. It has been shown to identify up to 90% of early-onset PE (EO-PE) cases, however, the detection rate of late-onset PE (LO-PE) remains low and the biomarkers PAPP-A and PlGF do not appear to significantly improve performance of screening for these cases compared to screening by maternal characteristics and medical history alone.

An abundance of biomarkers have been suggested and researched for the prediction of LO-PE and of these, matrix metalloproteinase 7 (MMP-7) has shown to be a potentially useful predictor with a sensitivity of 69% at a false positive rate (FPR) 20% at 8-16 weeks of pregnancy. Additionally, MAP appears to be a relatively good predictor for LO-PE at the same gestational age (GA). Ultimately, the search for more accurate biomarkers and prediction models for PE and especially for LO-PE remains relevant and necessary, both with regards to improving antenatal care and taking the necessary precautions for PE mothers, researching potential treatments, and gaining a better understanding of PE pathophysiology altogether.

This study will be a nested case-control study carried out as a sub-study of the larger multicenter study "Preeclampsia Screening in Denmark" (PRESIDE) comprising six major hospitals in Denmark, including Odense University Hospital (OUH). Throughout the time period September 2019 to March 2020, 1400 participants are expected to enroll in PRESIDE through OUH with the goal of validating the FMF screening algorithm in a Danish population. These women will be giving birth from March to June 2020. In our sub-study, the case group will consist of women diagnosed with PE after 34 weeks of gestation. With an expected late-onset PE incidence of 2,5%, the sample size of the case group will be n=35. The control group will include 165 participants who were not diagnosed with PE in their pregnancies.

All information regarding maternal characteristics and medical history are collected as part of standard procedure during first trimester screening for chromosomal abnormalities and is stored in theOUH fetal medicine database Astraia. Uterine artery flow values will be entered in Astraia along with these data. Mean arterial pressure (MAP) measurements will be automatically transferred to a REDCap database where all study data, including consent forms and outcome data, will be stored. For all participants, information regarding pregnancy and neonatal outcome will be collected from registers and individual patient files. The collected blood samples will be stored and analyzed after the child is born and hence, the PE risk will only be calculated after delivery. Venous blood will be sampled, and aliquots will be stored as part of a research biobank and a biobank for future research at the Department of Clinical Biochemistry and Pharmacology (KBF), OUH. The samples for measurement of MMP-7 will be taken from the biobank for future research and will be performed in the Biomarker Laboratory at the KBF research unit by an automated immunoassay analyzer system (Tritius) using a Human Total MMP-7 Quantikine ELISA Kit.

The cohort consists of pregnant women assigned to the Department of Obstetrics at Odense University Hospital for their first trimester nuchal translucency between September 2019 and March 2020; who are included/excluded according to the criteria; and who agree to enroll in the study. The potential participants will receive information about the study by e-boks (online communication platform) when they book their appointment for the first trimester scan and will be approached by project staff upon arrival to the department on the day of the scan. Those who agree to receive more information will be orally informed by project staff about the project and its implications. Each participant will provide written consent followed by blood sampling, MAP measurements, and ultrasound procedures.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1427

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Odense, Denmark, 5000
        • Odense University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Sampling Method

Probability Sample

Study Population

The cohort consists of pregnant women assigned to the Department of Obstetrics at Odense University Hospital for their first trimester nuchal translucency between September 2019 and March 2020; who are included/excluded according to the criteria below; and who agree to enroll in the study.

Description

Inclusion Criteria:

  • A planned first trimester nuchal translucency scan
  • Informed consent
  • Gestational age 11-14 weeks at the first trimester scan

Exclusion Criteria:

  • Age < 18 years
  • ≥ 2 fetuses
  • Participants must read and understand Danish or English

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Case-group
The case group will consist of women diagnosed with PE after 34 weeks of gestation.
Control-group
The control group will include 165 participants who were not diagnosed with PE in their pregnancies.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Late-onset preeclampsia
Time Frame: After delivery of the child, i.e. an average of 6 months from enrollment
Diagnosis of pre-eclampsia >34 weeks of pregnancy
After delivery of the child, i.e. an average of 6 months from enrollment

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Fetal growth restriction
Time Frame: After delivery of the child, i.e. an average of 6 months from enrollment
Neonates born with a birthweight < -21% or with signs of adaption to undernutrition
After delivery of the child, i.e. an average of 6 months from enrollment
Gestational hypertension
Time Frame: After delivery of the child, i.e. an average of 6 months from enrollment
Women who experienced new-onset hypertension in their pregnancies
After delivery of the child, i.e. an average of 6 months from enrollment
Apgar score
Time Frame: After delivery of the child, i.e. an average of 6 months from enrollment
Apgar scores of neonates born to the cohort
After delivery of the child, i.e. an average of 6 months from enrollment
Method of delivery
Time Frame: After delivery of the child, i.e. an average of 6 months from enrollment
Method of delivery (i.e. vaginal, elective Cesarean, emergency Cesarean) in the cohort
After delivery of the child, i.e. an average of 6 months from enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Southern Denmark

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Lene Sperling, M.D., PhD, Odense University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 13, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 23, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 28, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 3, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 19, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 16, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2019-031 PIKBF PRESIDE

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Preeclampsia

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings