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

Primary Purpose

Prenatal Disorder, Aneuploidy

Status
Active
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Traditional integrated prenatal screening
Second-tier Non-invasive prenatal screening (NIPS)
First-tier Non-invasive prenatal screening (NIPS)
Invasive prenatal testing for fetal aneuploidy
Sponsored by
CHU de Quebec-Universite Laval
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional screening trial for Prenatal Disorder focused on measuring Real life comparative effectiveness, Non-invasive prenatal screening, Fetal aneuploidy, Randomized controlled trial

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)FemaleAccepts Healthy Volunteers

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.

Sites / Locations

  • Kelowna Regional Fertility Center
  • Prince Rupert Regional Hospital
  • Children's & Women's Health Centre
  • CHU Ste-Justine
  • CHU de Québec - Université Laval
  • CIUSSS Côte-Nord

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Standard of care (2nd tier NIPS)

First-tier NIPS

Arm Description

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).

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).

Outcomes

Primary Outcome Measures

Gestational age at diagnosis
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

Secondary Outcome Measures

Gestational age at negative screening result
gestational age at final result in the sub-set of participants that have received a negative screening result
Gestational age at positive screening result
gestational age at final result in the sub-set of participants that have received a positive screening result
proportion of women with no results
proportion of women with no NIPS result at first and second attempt
numbers of days for women with false positive result of screen to wait for result of definite test
Difference between gestational age (in days) at first positive prenatal screening result and final negative screening result
Change in PROMIS-29 Score
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.
Change in PROMIS Emotional Distress - Anxiety - Short Form 8a Score
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.
Patient-Reported Experience Measure (PREM) - Score
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.
gestational age at termination of pregnancy
Gestational age at termination of pregnancy for participants having volountary termination
percentage of women undergoing invasive diagnostic testing
see outcome title

Full Information

First Posted
January 21, 2019
Last Updated
April 3, 2023
Sponsor
CHU de Quebec-Universite Laval
Collaborators
Genome Quebec, Genome British Columbia, Genome Alberta, Ontario Research Fund, Laval University, St. Justine's Hospital, Ottawa Hospital Research Institute, McGill University, University of British Columbia, University of Alberta, Genome Canada, Canadian Institutes of Health Research (CIHR)
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1. Study Identification

Unique Protocol Identification Number
NCT03831256
Brief Title
PErsonalized Genomics for Prenatal Abnormalities Screening USing Maternal Blood
Acronym
PEGASUS-2
Official Title
PErsonalized Genomics for Prenatal Abnormalities Screening USing Maternal Blood : Towards First Tier Screening and Beyond
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 13, 2020 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
CHU de Quebec-Universite Laval
Collaborators
Genome Quebec, Genome British Columbia, Genome Alberta, Ontario Research Fund, Laval University, St. Justine's Hospital, Ottawa Hospital Research Institute, McGill University, University of British Columbia, University of Alberta, Genome Canada, Canadian Institutes of Health Research (CIHR)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prenatal Disorder, Aneuploidy
Keywords
Real life comparative effectiveness, Non-invasive prenatal screening, Fetal aneuploidy, Randomized controlled trial

7. Study Design

Primary Purpose
Screening
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Open-label prospective comparative-effectiveness (utility) randomised trial between first-tier NIPS and the standard of care (2nd-tier NIPS).
Masking
None (Open Label)
Allocation
Randomized
Enrollment
7849 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Standard of care (2nd tier NIPS)
Arm Type
Active Comparator
Arm Description
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).
Arm Title
First-tier NIPS
Arm Type
Experimental
Arm Description
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).
Intervention Type
Diagnostic Test
Intervention Name(s)
Traditional integrated prenatal screening
Other Intervention Name(s)
IPS
Intervention Description
biochemical prenatal screening with or without nuchal translucency by US
Intervention Type
Diagnostic Test
Intervention Name(s)
Second-tier Non-invasive prenatal screening (NIPS)
Other Intervention Name(s)
second tier non-invasive prenatal testing (NIPT)
Intervention Description
genomics based NIPS after a positive traditional prenatal screen
Intervention Type
Diagnostic Test
Intervention Name(s)
First-tier Non-invasive prenatal screening (NIPS)
Other Intervention Name(s)
first tier NIPT, Universal NIPS, Universal NIPT
Intervention Description
genomics based NIPS at first trimester
Intervention Type
Diagnostic Test
Intervention Name(s)
Invasive prenatal testing for fetal aneuploidy
Intervention Description
amniocentesis or chorionic villi sampling (CVS)
Primary Outcome Measure Information:
Title
Gestational age at diagnosis
Description
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
Time Frame
Up to 24 weeks of gestational age
Secondary Outcome Measure Information:
Title
Gestational age at negative screening result
Description
gestational age at final result in the sub-set of participants that have received a negative screening result
Time Frame
Up to 24 weeks of gestational age
Title
Gestational age at positive screening result
Description
gestational age at final result in the sub-set of participants that have received a positive screening result
Time Frame
Up to 24 weeks of gestational age
Title
proportion of women with no results
Description
proportion of women with no NIPS result at first and second attempt
Time Frame
Up to 24 weeks of gestational age
Title
numbers of days for women with false positive result of screen to wait for result of definite test
Description
Difference between gestational age (in days) at first positive prenatal screening result and final negative screening result
Time Frame
Up to 24 weeks of gestational age
Title
Change in PROMIS-29 Score
Description
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.
Time Frame
At weeks of gestation 10-13, week 16 and week 22
Title
Change in PROMIS Emotional Distress - Anxiety - Short Form 8a Score
Description
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.
Time Frame
At weeks of gestation 10-13, 16 and 22
Title
Patient-Reported Experience Measure (PREM) - Score
Description
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.
Time Frame
At 22 weeks of gestation
Title
gestational age at termination of pregnancy
Description
Gestational age at termination of pregnancy for participants having volountary termination
Time Frame
Up to 24 weeks of gestational age
Title
percentage of women undergoing invasive diagnostic testing
Description
see outcome title
Time Frame
Up to 24 weeks of gestational age

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sylvie Langlois, MD FRCPC
Organizational Affiliation
University of British Columbia
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Francois Rousseau, MD MSc FRCPC
Organizational Affiliation
CHU de Québec - Université Laval
Official's Role
Principal Investigator
Facility Information:
Facility Name
Kelowna Regional Fertility Center
City
Kelowna
State/Province
British Columbia
ZIP/Postal Code
V1Y 1P2
Country
Canada
Facility Name
Prince Rupert Regional Hospital
City
Prince Rupert
State/Province
British Columbia
ZIP/Postal Code
V8J 2A6
Country
Canada
Facility Name
Children's & Women's Health Centre
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6H 3N1
Country
Canada
Facility Name
CHU Ste-Justine
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1C5
Country
Canada
Facility Name
CHU de Québec - Université Laval
City
Québec City
State/Province
Quebec
ZIP/Postal Code
G1L3L5
Country
Canada
Facility Name
CIUSSS Côte-Nord
City
Sept-Îles
State/Province
Quebec
ZIP/Postal Code
G4R 0N9
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
29125628
Citation
Badeau M, Lindsay C, Blais J, Nshimyumukiza L, Takwoingi Y, Langlois S, Legare F, Giguere Y, Turgeon AF, Witteman W, Rousseau F. Genomics-based non-invasive prenatal testing for detection of fetal chromosomal aneuploidy in pregnant women. Cochrane Database Syst Rev. 2017 Nov 10;11(11):CD011767. doi: 10.1002/14651858.CD011767.pub2.
Results Reference
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PErsonalized Genomics for Prenatal Abnormalities Screening USing Maternal Blood

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