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

• ClinicalTrials.gov Identifier: NCT03831256
• Recruitment Status: Recruiting
• First Posted: February 5, 2019
• Last Update Posted: January 31, 2022
• 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)
• Information provided by (Responsible Party): François Rousseau, CHU de Quebec-Universite Laval

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.

Condition or disease	Intervention/treatment	Phase
Prenatal Disorder; Aneuploidy	Diagnostic Test: Traditional integrated prenatal screening; Diagnostic Test: Second-tier Non-invasive prenatal screening (NIPS); Diagnostic Test: First-tier Non-invasive prenatal screening (NIPS); Diagnostic Test: Invasive prenatal testing for fetal aneuploidy	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 7500 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention 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)
• Primary Purpose: Screening
• Official Title: PErsonalized Genomics for Prenatal Abnormalities Screening USing Maternal Blood : Towards First Tier Screening and Beyond
• Actual Study Start Date: January 13, 2020
• Estimated Primary Completion Date: March 31, 2023
• Estimated Study Completion Date: March 31, 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. 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

Secondary Outcome Measures :

1. 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
2. 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
3. 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
4. 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
5. 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.
6. 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.
7. 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.

8. 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
9. percentage of women undergoing invasive diagnostic testing [ Time Frame: Up to 24 weeks of gestational age ]
   see outcome title

Eligibility Criteria

• Ages Eligible for Study: 19 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Contacts

Contact: Sylvie Langlois, MD FRCPC; 604-875-2823; slanglois@cw.bc.ca

Contact: Francois Rousseau, MD MSc FRCPC; 418-525-4470; francois.rousseau@fmed.ulaval.ca

Locations

Canada, British Columbia

Kelowna Regional Fertility Center; Recruiting

Kelowna, British Columbia, Canada, V1Y 1P2

Principal Investigator: Sylvie Langlois, MD FRCPC

Prince Rupert Regional Hospital; Not yet recruiting

Prince Rupert, British Columbia, Canada, V8J 2A6

Principal Investigator: Sylvie Langlois, MD FRCPC

Children's & Women's Health Centre; Recruiting

Vancouver, British Columbia, Canada, V6H 3N1

Contact: Sylvie Langlois, MD SLanglois@cw.bc.ca

Principal Investigator: Sylvie Langlois, MD FRCPC

Canada, Quebec

CHU Ste-Justine; Recruiting

Montreal, Quebec, Canada, H3T 1C5

Contact: Francois Audibert, MD, MSc francois.audibert@umontreal.ca

Principal Investigator: Francois Audibert, MD,MSc,FRCSC

CHU de Québec - Université Laval; Recruiting

Québec City, Quebec, Canada, G1L3L5

Contact: François Rousseau, MD 418-525-4470 francois.rousseau@fmed.ulaval.ca

Contact: Jean-Claude Forest, MD PhD 418-525-4438 jean-clause.forest@chudequebec.ca

Principal Investigator: Emmanuel Bujold, MD MSc FRCSC

CIUSSS Côte-Nord; Not yet recruiting

Sept-Îles, Quebec, Canada, G4R 0N9

Contact: Martine Simard, MD FRCSC +1 (418) 962-9761 msim64@hotmail.com

Sponsors and Collaborators

CHU de Quebec-Universite Laval

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)

Investigators

• Principal Investigator: Sylvie Langlois, MD FRCPC; University of British Columbia
• Principal Investigator: Francois Rousseau, MD MSc FRCPC; CHU de Québec - Université Laval

More Information

Publications:

Badeau M, Lindsay C, Blais J, Nshimyumukiza L, Takwoingi Y, Langlois S, Légaré F, Giguère 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:CD011767. doi: 10.1002/14651858.CD011767.pub2. Review.

• Responsible Party: François Rousseau, Professor-doctor, CHU de Quebec-Universite Laval
• ClinicalTrials.gov Identifier: NCT03831256
• Other Study ID Numbers: SIRUL 118984
• First Posted: February 5, 2019
• Last Update Posted: January 31, 2022
• Last Verified: January 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by François Rousseau, CHU de Quebec-Universite Laval:

Real life comparative effectiveness; Non-invasive prenatal screening; Fetal aneuploidy; Randomized controlled trial

Additional relevant MeSH terms:

Aneuploidy; Chromosome Aberrations; Pathologic Processes