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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Centre Hospitalier Universitaire de Québec, CHU de Québec
Sponsor:
Collaborators:
Laval University
Genome Canada
Genome Quebec
Genome British Columbia
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Québec, CHU de Québec
ClinicalTrials.gov Identifier:
NCT01925742
First received: August 16, 2013
Last updated: July 21, 2014
Last verified: July 2014
  Purpose

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 Intervention
Trisomy 21
Trisomy 18
Trisomy 13
Other: Integrated prenatal screening for Down's syndrome
Other: Serum QUAD Assay for aneuploidy screening
Other: Targeted NIPT assay using ccfDNA in maternal blood
Other: Un-targeted NIPT assay using ccfDNA in maternal blood
Other: Harmony™ Test (Ariosa Diagnostics)

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Screening
Official Title: PEGASUS: PErsonalized Genomics for Prenatal Aneuploidy Screening USing Maternal Blood

Resource links provided by NLM:


Further study details as provided by Centre Hospitalier Universitaire de Québec, CHU de Québec:

Primary Outcome Measures:
  • Number of cases with Fetal trisomy 21, 18 or 13 [ Time Frame: 6 weeks after the delivery date ] [ Designated as safety issue: No ]
    Only pregnant women will be recruited, fetal outcome will be assessed by fetal karyotype or at or after delivery.


Secondary Outcome Measures:
  • Number of women with assay failure [ Time Frame: At end of pregnancy. ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Overall costs of screening algorithm [ Time Frame: 6 weeks after delivery ] [ Designated as safety issue: No ]

Estimated Enrollment: 5600
Study Start Date: November 2013
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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; Targeted NIPT assay using ccfDNA in maternal blood; Untargeted 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 Name: First trimester QUAD prenatal screening assay
Other: Targeted 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
  • Targeted NIPD
  • Non-invasive prenatal testing
  • Non-invasive prenatal diagnosis
Other: Un-targeted 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 Name: 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; Targeted NIPT assay using ccfDNA in maternal blood; Untargeted 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 Name: First trimester QUAD prenatal screening assay
Other: Targeted 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
  • Targeted NIPD
  • Non-invasive prenatal testing
  • Non-invasive prenatal diagnosis
Other: Un-targeted 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 Name: DANSR Assay

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).

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01925742

Contacts
Contact: Sylvie Langlois, MD FRCPC slanglois@cw.bc.ca

Locations
Canada, Alberta
Foothills Medical Centre Recruiting
Calgary, Alberta, Canada, T2N 2T9
Contact: Jo-Ann Johnson, MD       Joann.Johnson@albertahealthservices.ca   
Principal Investigator: Jo-Ann Johnson, MD, FRCSC         
Canada, British Columbia
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, Ontario
The Ottawa Hospital Recruiting
Ottawa, Ontario, Canada, K1H 8L6
Contact: Mark Walker, MD, MSc       mwalker@ohri.ca   
Contact: Ruth R White, RN, BScN       rwhite@Ottawahospital.on.ca   
Principal Investigator: Mark Walker, 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 Recruiting
Quebec City, Quebec, Canada, G1L3L5
Contact: Jean Gekas, MD, PhD       jean.gekas@mail.chuq.qc.ca   
Contact: Emmanuel Bujold, MD MSc       emmanuel.bujold@crchul.ulaval.ca   
Principal Investigator: Jean Gekas, MD, PhD         
Sponsors and Collaborators
Centre Hospitalier Universitaire de Québec, CHU de Québec
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
  More Information

No publications provided

Responsible Party: Centre Hospitalier Universitaire de Québec, CHU de Québec
ClinicalTrials.gov Identifier: NCT01925742     History of Changes
Other Study ID Numbers: 2014-1236; SIRUL-102531, B13-06-1236
Study First Received: August 16, 2013
Last Updated: July 21, 2014
Health Authority: Canada : Genome Canada

Keywords provided by Centre Hospitalier Universitaire de Québec, CHU de Québec:
Fetal aneuploidy

Additional relevant MeSH terms:
Aneuploidy
Down Syndrome
Trisomy
Chromosome Aberrations
Pathologic Processes
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn
Chromosome Duplication

ClinicalTrials.gov processed this record on August 19, 2014