PErsonalized Genomics for Prenatal Abnormalities Screening USing Maternal Blood

Aneuploidy Clinical Trial

— PEGASUS-2  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03831256
• Other study ID #: SIRUL 118984
• Status: Active, not recruiting
• Phase: N/A
• Start date: January 13, 2020
• Est. completion date: December 31, 2023

Study information

• Verified date: April 2023
• Source: CHU de Quebec-Universite Laval
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 7849
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 19 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Aneuploidy
• Prenatal Disorder

Intervention

Diagnostic Test:
• Traditional integrated prenatal screening
biochemical prenatal screening with or without nuchal translucency by US
• Second-tier Non-invasive prenatal screening (NIPS)
genomics based NIPS after a positive traditional prenatal screen
• First-tier Non-invasive prenatal screening (NIPS)
genomics based NIPS at first trimester
• Invasive prenatal testing for fetal aneuploidy
amniocentesis or chorionic villi sampling (CVS)

Locations

Country	Name	City	State
Canada	Kelowna Regional Fertility Center	Kelowna	British Columbia
Canada	CHU Ste-Justine	Montreal	Quebec
Canada	Prince Rupert Regional Hospital	Prince Rupert	British Columbia
Canada	CHU de Québec - Université Laval	Québec City	Quebec
Canada	CIUSSS Côte-Nord	Sept-Îles	Quebec
Canada	Children's & Women's Health Centre	Vancouver	British Columbia

Sponsors (13)

Lead Sponsor	Collaborator
CHU de Quebec-Universite Laval	Canadian Institutes of Health Research (CIHR), Genome Alberta, Genome British Columbia, Genome Canada, Genome Quebec, Laval University, McGill University, Ontario Research Fund, Ottawa Hospital Research Institute, St. Justine's Hospital, University of Alberta, University of British Columbia

Country where clinical trial is conducted

Canada, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Up to 24 weeks of gestational age
Secondary	Gestational age at negative screening result	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
Secondary	Gestational age at positive screening result	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
Secondary	proportion of women with no results	proportion of women with no NIPS result at first and second attempt	Up to 24 weeks of gestational age
Secondary	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	Up to 24 weeks of gestational age
Secondary	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.	At weeks of gestation 10-13, week 16 and week 22
Secondary	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.	At weeks of gestation 10-13, 16 and 22
Secondary	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.	At 22 weeks of gestation
Secondary	gestational age at termination of pregnancy	Gestational age at termination of pregnancy for participants having volountary termination	Up to 24 weeks of gestational age
Secondary	percentage of women undergoing invasive diagnostic testing	see outcome title	Up to 24 weeks of gestational age