- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01925742
Study of the Efficacy of New Non-invasive Prenatal Tests for Screening for Fetal Trisomies Using Maternal Blood (PEGASUS)
PEGASUS: PErsonalized Genomics for Prenatal Aneuploidy Screening USing Maternal Blood
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Alberta
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Calgary, Alberta, Canada, T2N 2T9
- Foothills Medical Centre
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British Columbia
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Vancouver, British Columbia, Canada, V6H 3N1
- Children's & Women's Health Centre
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Ontario
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Ottawa, Ontario, Canada, K1H 8L6
- The Ottawa Hospital
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Quebec
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Montreal, Quebec, Canada, H3T 1C5
- CHU Ste-Justine
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Quebec City, Quebec, Canada, G1L3L5
- CHU de Québec
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Screening
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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)
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Analysis of several serum biochemical markers, and fetal nuchal translucency by ultrasound, with computation of an individual risk of fetal aneuploidy.
Other Names:
Series of biochemical markers with results integrated into a computational estimate of risk of fetal aneuploidy
Other Names:
Analysis by next-generation sequencing of ccfDNA (circulating cell-free DNA) from maternal blood, using a targeted NIPT assay.
Other Names:
Analysis by next-generation sequencing of ccfDNA (circulating cell-free DNA) from maternal blood, using an un-targeted NIPT assay.
Other Names:
Test that is commercially available (Ariosa Diagnostics).
(will be used for benchmarking purposes in a subset of each arm)
Other Names:
|
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)
|
Analysis of several serum biochemical markers, and fetal nuchal translucency by ultrasound, with computation of an individual risk of fetal aneuploidy.
Other Names:
Series of biochemical markers with results integrated into a computational estimate of risk of fetal aneuploidy
Other Names:
Analysis by next-generation sequencing of ccfDNA (circulating cell-free DNA) from maternal blood, using a targeted NIPT assay.
Other Names:
Analysis by next-generation sequencing of ccfDNA (circulating cell-free DNA) from maternal blood, using an un-targeted NIPT assay.
Other Names:
Test that is commercially available (Ariosa Diagnostics).
(will be used for benchmarking purposes in a subset of each arm)
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of cases with Fetal trisomy 21, 18 or 13
Time Frame: 6 weeks after the delivery date
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Only pregnant women will be recruited, fetal outcome will be assessed by fetal karyotype or at or after delivery.
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6 weeks after the delivery date
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Number of women with assay failure
Time Frame: At end of pregnancy.
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At end of pregnancy.
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Other Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Overall costs of screening algorithm
Time Frame: 6 weeks after delivery
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6 weeks after delivery
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Francois Rousseau, MD MSc FRCPC, Universite Laval and CHU de Quebec
Publications and helpful links
General Publications
- Fibke C, Giroux S, Caron A, Starks E, Parker JDK, Swanson L, Jouan L, Langlois S, Rouleau G, Rousseau F, Karsan A. Effect of preexamination conditions in a centralized-testing model of non-invasive prenatal screening. Clin Chem Lab Med. 2021 Nov 11;60(2):183-190. doi: 10.1515/cclm-2021-0652. Print 2022 Jan 27.
- Rousseau F, Langlois S, Johnson JA, Gekas J, Bujold E, Audibert F, Walker M, Giroux S, Caron A, Clement V, Blais J, MacLeod T, Moore R, Gauthier J, Jouan L, Laporte A, Diallo O, Parker J, Swanson L, Zhao Y, Labelle Y, Giguere Y, Forest JC, Little J, Karsan A, Rouleau G. Prospective head-to-head comparison of accuracy of two sequencing platforms for screening for fetal aneuploidy by cell-free DNA: the PEGASUS study. Eur J Hum Genet. 2019 Nov;27(11):1701-1715. doi: 10.1038/s41431-019-0443-0. Epub 2019 Jun 23.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Heart Diseases
- Cardiovascular Diseases
- Nervous System Diseases
- Neurologic Manifestations
- Neurobehavioral Manifestations
- Congenital Abnormalities
- Genetic Diseases, Inborn
- Intellectual Disability
- Heart Defects, Congenital
- Cardiovascular Abnormalities
- Abnormalities, Multiple
- Chromosome Disorders
- Chromosome Aberrations
- Aneuploidy
- Chromosome Duplication
- Down Syndrome
- Trisomy
- Trisomy 13 Syndrome
- Trisomy 18 Syndrome
Other Study ID Numbers
- 2014-1236; SIRUL-102531
- B13-06-1236 (Other Identifier: Université Laval)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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