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PEGASUS: Study of the Efficacy of New Non-invasive Prenatal Tests for Screening for Fetal Trisomies Using Maternal Blood

Sponsor
CHU de Quebec-Universite Laval (Other)
Overall Status
Completed
CT.gov ID
NCT01925742
Collaborator
Laval University (Other), Genome Canada (Other), Genome Quebec (Other), Genome British Columbia (Industry), Canadian Institutes of Health Research (CIHR) (Other)
3,819
Enrollment
5
Locations
2
Arms
43
Duration (Months)
763.8
Patients Per Site
17.8
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Each year, 450,000 Canadian women become pregnant and, as a result of their participation in prenatal screening for Down syndrome, approximately 10,000 of them will have an amniocentesis (i.e. sampling of liquid surrounding the fetus) and of those, 315 will be found to carry a baby with Down syndrome and 70 normal pregnancies will be lost from complications of the procedure. It has been discovered recently that, during pregnancy, there is fetal DNA in maternal blood in sufficient quantities to be analysed and methods have been proposed to detect the presence or not of a fetus with Down syndrome using maternal blood. The introduction of genomic blood testing as proposed in the context of this project could lead to increased detection of Down syndrome, less invasive screening with 9700 amniocentesis avoided each year in Canada, improving the peace of mind of pregnant women, and preventing the accidental loss of 70 normal fetuses, at a lower overall cost than current practice. However, these methods still need to be validated before being appropriately introduced in routine care.

The study hypothesis is that new genomics-based non-invasive methods using fetal-DNA in maternal blood during pregnancy can be more effective than current prenatal screening methods for fetal aneuploidy.

This project will carry out an independent study that will validate the performance and utility of different new genomic technologies for screening in pregnant women using maternal blood. The team of researchers will compare the real-life performance of different non-invasive assays and strategies to screen for fetal aneuploidy, and identify an evidence-based cost-effective approach for implementation of this new technology in the Canadian health care system. The deliverables of this project will enable decision makers, pregnant women and their partner to make informed choices pertaining to prenatal genetic screening and diagnosis, such as screening for Down syndrome, and reduce the risk to pregnancies associated with amniocentesis.

Condition or Disease Intervention/Treatment Phase
  • Other: Integrated prenatal screening for Down's syndrome
  • Other: Serum QUAD Assay for aneuploidy screening
  • Other: Semiconductor MPSS NIPT assay using ccfDNA in maternal blood
  • Other: Optical-based MPSS NIPT assay using ccfDNA in maternal blood
  • Other: Harmony™ Test (Ariosa Diagnostics)
 N/A

Detailed Description

The present study is a real life comparative effectiveness study that will compare the performances and costs of several prenatal screening modalities for fetal aneuploidy (see interventions).

Study Design

Study Type:
Interventional
Actual Enrollment :
3819 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Screening
Official Title:
PEGASUS: PErsonalized Genomics for Prenatal Aneuploidy Screening USing Maternal Blood
Study Start Date :
Nov 1, 2013
Actual Primary Completion Date :
Jun 1, 2017
Actual Study Completion Date :
Jun 1, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: Low Risk of aneuploidy

Integrated prenatal screening for Down's syndrome (with follow-up fetal karyotype if positive); Serum QUAD Assay for aneuploidy screening; Semiconductor MPSS NIPT assay using ccfDNA in maternal blood; Optical-based MPSS NIPT assay using ccfDNA in maternal blood; Harmony™ Test (Ariosa Diagnostics)

Other: Integrated prenatal screening for Down's syndrome
Analysis of several serum biochemical markers, and fetal nuchal translucency by ultrasound, with computation of an individual risk of fetal aneuploidy.
Other Names:
  • IPS
  • Prenatal serum screening
  • Aneuploidy screening
  • Down's syndrome screening
  • Downs' syndrome screening

    • Other: Serum QUAD Assay for aneuploidy screening
    Series of biochemical markers with results integrated into a computational estimate of risk of fetal aneuploidy
    Other Names:
  • First trimester QUAD prenatal screening assay

    • Other: Semiconductor MPSS NIPT assay using ccfDNA in maternal blood
    Analysis by next-generation sequencing of ccfDNA (circulating cell-free DNA) from maternal blood, using a targeted NIPT assay.
    Other Names:
  • NIPD
  • MPSS
  • Non-invasive prenatal testing
  • Non-invasive prenatal diagnosis

    • Other: Optical-based MPSS NIPT assay using ccfDNA in maternal blood
    Analysis by next-generation sequencing of ccfDNA (circulating cell-free DNA) from maternal blood, using an un-targeted NIPT assay.
    Other Names:
  • NIPD
  • MPSS
  • Un-Targeted NIPD
  • Non-invasive prenatal testing
  • Non-invasive prenatal diagnosis

    • Other: Harmony™ Test (Ariosa Diagnostics)
    Test that is commercially available (Ariosa Diagnostics). (will be used for benchmarking purposes in a subset of each arm)
    Other Names:
  • DANSR Assay

    		•
    Experimental: High risk of aneuploidy

    Integrated prenatal screening for Down's syndrome (with follow-up fetal karyotype if positive); Serum QUAD Assay for aneuploidy screening; Semiconductor MPSS NIPT assay using ccfDNA in maternal blood; Optical-based MPSS NIPT assay using ccfDNA in maternal blood; Harmony™ Test (Ariosa Diagnostics) (subset)

    Other: Integrated prenatal screening for Down's syndrome
    Analysis of several serum biochemical markers, and fetal nuchal translucency by ultrasound, with computation of an individual risk of fetal aneuploidy.
    Other Names:
  • IPS
  • Prenatal serum screening
  • Aneuploidy screening
  • Down's syndrome screening
  • Downs' syndrome screening

    • Other: Serum QUAD Assay for aneuploidy screening
    Series of biochemical markers with results integrated into a computational estimate of risk of fetal aneuploidy
    Other Names:
  • First trimester QUAD prenatal screening assay

    • Other: Semiconductor MPSS NIPT assay using ccfDNA in maternal blood
    Analysis by next-generation sequencing of ccfDNA (circulating cell-free DNA) from maternal blood, using a targeted NIPT assay.
    Other Names:
  • NIPD
  • MPSS
  • Non-invasive prenatal testing
  • Non-invasive prenatal diagnosis

    • Other: Optical-based MPSS NIPT assay using ccfDNA in maternal blood
    Analysis by next-generation sequencing of ccfDNA (circulating cell-free DNA) from maternal blood, using an un-targeted NIPT assay.
    Other Names:
  • NIPD
  • MPSS
  • Un-Targeted NIPD
  • Non-invasive prenatal testing
  • Non-invasive prenatal diagnosis

    • Other: Harmony™ Test (Ariosa Diagnostics)
    Test that is commercially available (Ariosa Diagnostics). (will be used for benchmarking purposes in a subset of each arm)
    Other Names:
  • DANSR Assay

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of cases with Fetal trisomy 21, 18 or 13 [6 weeks after the delivery date]

      Only pregnant women will be recruited, fetal outcome will be assessed by fetal karyotype or at or after delivery.

    Secondary Outcome Measures

    1. Number of women with assay failure [At end of pregnancy.]

    Other Outcome Measures

    1. Overall costs of screening algorithm [6 weeks after delivery]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    19 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria (High risk arm):

    • women 19 years or older between 10 weeks and 23 weeks 6 days gestation undergoing amniocentesis or CVS for:

    • positive prenatal screen;

    • abnormal ultrasound

    • previous pregnancy with trisomy

    • patient or partner carrier of Robertsonian translocation involving chr 21

    • positive NIPT result

    • Maternal age 40 or more

    Inclusion Criteria (Low risk arm):
    • women 19 years and older who are 10 and 13 weeks 6 days gestation based on dating ultrasound (CRL) and are undergoing screening for Down syndrome (first trimester combined, SIPS or IPS)
    Exclusion Criteria:

    • women with multiple gestations

    • women with twin demise (spontaneous or elective) at any gestational age

    • women with active or history of malignancy

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Foothills Medical Centre Calgary Alberta Canada T2N 2T9
    2 Children's & Women's Health Centre Vancouver British Columbia Canada V6H 3N1
    3 The Ottawa Hospital Ottawa Ontario Canada K1H 8L6
    4 CHU Ste-Justine Montreal Quebec Canada H3T 1C5
    5 CHU de Québec Quebec City Quebec Canada G1L3L5

    Sponsors and Collaborators

    • CHU de Quebec-Universite Laval
    • Laval University
    • Genome Canada
    • Genome Quebec
    • Genome British Columbia
    • Canadian Institutes of Health Research (CIHR)

    Investigators

    • Principal Investigator: Francois Rousseau, MD MSc FRCPC, Universite Laval and CHU de Quebec
    • Principal Investigator: Sylvie Langlois, MD FRCPC, University of British Columbia

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    CHU de Quebec-Universite Laval
    ClinicalTrials.gov Identifier:
    NCT01925742
    Other Study ID Numbers:
    • 2014-1236; SIRUL-102531
    • B13-06-1236
    First Posted:
    Aug 20, 2013
    Last Update Posted:
    Feb 22, 2018
    Last Verified:
    Apr 1, 2016
    Keywords provided by CHU de Quebec-Universite Laval
    Fetal aneuploidy
    Additional relevant MeSH terms:
    Down Syndrome
    Trisomy 13 Syndrome
    Trisomy 18 Syndrome
    Trisomy

    Study Results

    No Results Posted as of Feb 22, 2018