PErsonalized Genomics for Prenatal Abnormalities Screening USing Maternal Blood (PEGASUS-2)

April 3, 2023 updated by: François Rousseau, CHU de Quebec-Universite Laval

PErsonalized Genomics for Prenatal Abnormalities Screening USing Maternal Blood : Towards First Tier Screening and Beyond

This project aims to provide high- quality evidence to inform decisions by health care organisations about using first-tier non-invasive prenatal screening (NIPS) to replace traditional screening tests for trisomy 21, and potentially to screen for other fetal chromosome anomalies. We will compare the current screening approach of second-tier NIPS with the use of first-tier NIPS in a large cohort of pregnant women.

Study Overview

Detailed Description

There is some data on the performance of NIPS as a first tier screening test but our systematic review has shown that no trial comparing the effectiveness (utility) of 2nd-tier NIPS with that of first-tier NIPS has been published . Further it is important for health care decision makers to have evidence produced in Canada since the geographical context of healthcare can affect uptake as well as patient decision and thus their healthcare trajectories. There is a need for a trial that is between an explanatory trial and a pragmatic trial to provide the types of answer that we aim to document in the present state of knowledge on NIPS-based screening strategies in Canada. Our Objective is to perform a pan-Canadian large-scale comparative utility (clinical outcomes) study of first-tier NIPS (expanded or not) as compared to the new standard of care (NIPS as a 2nd tier test performed much later during pregnancy and only in high risk pregnancies).

Study Type

Interventional

Enrollment (Actual)

7849

Phase

  • Not Applicable

Contacts and Locations

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

Study Contact

Study Contact Backup

Study Locations

    • British Columbia
      • Kelowna, British Columbia, Canada, V1Y 1P2
        • Kelowna Regional Fertility Center
      • Prince Rupert, British Columbia, Canada, V8J 2A6
        • Prince Rupert Regional Hospital
      • Vancouver, British Columbia, Canada, V6H 3N1
        • Children's & Women's Health Centre
    • Quebec
      • Montreal, Quebec, Canada, H3T 1C5
        • CHU Ste-Justine
      • Québec City, Quebec, Canada, G1L3L5
        • CHU de Québec - Université Laval
      • Sept-Îles, Quebec, Canada, G4R 0N9
        • CIUSSS Côte-Nord

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

Ages Eligible for Study

19 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Pregnant women 19 years or older wanting prenatal screening
  • 10-13+6 wks determined by dating ultrasound or last menstrual period.
  • Not intending to pursue self pay NIPT

Exclusion Criteria:

  • Known fetal anomaly at the time of recruitment
  • Multiple gestation
  • Known twin demise
  • Planned CVS or amnio for known genetic condition.

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

  • Primary Purpose: Screening
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Standard of care (2nd tier NIPS)
For the standard-of-care arm (2nd tier NIPS) women will undergo Traditional integrated prenatal screening i.e. traditional biochemical (+/- NT) and those with a positive screen for T21 or T18 will be offered Second-tier Non-invasive prenatal screening (NIPS) (for T21, T18, T13) or Invasive prenatal testing for fetal aneuploidy. Ultrasound examination in first and second trimester will be done based on clinical care practice ordered by health care provider. Pregnant women with a positive NIPS test will be offered Invasive prenatal testing for fetal aneuploidy (fetal chromosome analysis).
biochemical prenatal screening with or without nuchal translucency by US
Other Names:
  • IPS
genomics based NIPS after a positive traditional prenatal screen
Other Names:
  • second tier non-invasive prenatal testing (NIPT)
amniocentesis or chorionic villi sampling (CVS)
Experimental: First-tier NIPS
For the intervention arm (1st tier NIPS) women will receive First-tier Non-invasive prenatal screening (NIPS) i.e. provide a blood sample between 10-13+5 weeks gestation with NIPS results within 7 - 10 days of sample collection. Ultrasound examination in first and second trimester will be done based on clinical care practice ordered by health care provider. In case of a failed NIPS test (expected to be between 2% and 4% of samples), a new blood sample will be drawn for NIPS retest as well as for a traditional SIPS(serum integrated prenatal screening) or QUAD(quadruple marker prenatal screening) screen (depending on gestational age). Pregnant women with a positive NIPS test will be offered Invasive prenatal testing for fetal aneuploidy (fetal chromosome analysis).
amniocentesis or chorionic villi sampling (CVS)
genomics based NIPS at first trimester
Other Names:
  • first tier NIPT, Universal NIPS, Universal NIPT

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Gestational age at diagnosis
Time Frame: Up to 24 weeks of gestational age
gestational age at final result in the sub-set of participants that have received a positive NIPS result and that have been offered diagnostic testing
Up to 24 weeks of gestational age

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Gestational age at negative screening result
Time Frame: Up to 24 weeks of gestational age
gestational age at final result in the sub-set of participants that have received a negative screening result
Up to 24 weeks of gestational age
Gestational age at positive screening result
Time Frame: Up to 24 weeks of gestational age
gestational age at final result in the sub-set of participants that have received a positive screening result
Up to 24 weeks of gestational age
proportion of women with no results
Time Frame: Up to 24 weeks of gestational age
proportion of women with no NIPS result at first and second attempt
Up to 24 weeks of gestational age
numbers of days for women with false positive result of screen to wait for result of definite test
Time Frame: Up to 24 weeks of gestational age
Difference between gestational age (in days) at first positive prenatal screening result and final negative screening result
Up to 24 weeks of gestational age
Change in PROMIS-29 Score
Time Frame: At weeks of gestation 10-13, week 16 and week 22
The PROMIS-29 assesses seven health domains: physical function, anxiety, depression, fatigue, sleep disturbance, pain interference, and ability to participate in social roles and activities. Each of the seven domains has four questions which are scored on a five-point Likert scale. The PROMIS-29 scales will be scored using a T-score metric method available at the Assessment Center website (http://assessmentcenter.net). A score of 50 points represents the population average for each scale, and 10 points represent one standard deviation. Higher scores mean more of the specific scale's construct, which may indicate a desirable or an undesirable outcome. The assessment will be done at recruitment (10-13 weeks of gestation) and at week 16 and week 22 of gestation.
At weeks of gestation 10-13, week 16 and week 22
Change in PROMIS Emotional Distress - Anxiety - Short Form 8a Score
Time Frame: At weeks of gestation 10-13, 16 and 22
The PROMIS-Anxiety short form assesses anxiety with 8 questions. The form includes 8 items and uses a scale of 1-5 (1=Never, 2=Almost never, 3= Sometimes, 4=Often, 5=Almost always). The raw score is the sum of the points for each response. A higher than average raw score indicates higher than average anxiety. A higher score represents higher levels of anxiety. The assessment will be done at recruitment (10-13 weeks of gestation) and at week 16 and week 22 of gestation.
At weeks of gestation 10-13, 16 and 22
Patient-Reported Experience Measure (PREM) - Score
Time Frame: At 22 weeks of gestation

A 17-questions validated PREM questionnaire on pregnancy experience that measures three dimensions - type of prenatal care received and test results (seven questions), pregnancy visits (four questions (scales 1-5) and prenatal screening experience (six questions).

A profile score by looking at frequencies of responses for each item will be used.

At 22 weeks of gestation
gestational age at termination of pregnancy
Time Frame: Up to 24 weeks of gestational age
Gestational age at termination of pregnancy for participants having volountary termination
Up to 24 weeks of gestational age
percentage of women undergoing invasive diagnostic testing
Time Frame: Up to 24 weeks of gestational age
see outcome title
Up to 24 weeks of gestational age

Collaborators and Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

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)

January 13, 2020

Primary Completion (Anticipated)

December 31, 2023

Study Completion (Anticipated)

December 31, 2023

Study Registration Dates

First Submitted

January 21, 2019

First Submitted That Met QC Criteria

February 4, 2019

First Posted (Actual)

February 5, 2019

Study Record Updates

Last Update Posted (Actual)

April 4, 2023

Last Update Submitted That Met QC Criteria

April 3, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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.

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