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

NCT ID: NCT01925742

Last Updated: 2018-02-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 3819 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-11-30
• Study Completion Date: 2017-06-30

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.

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).

Conditions

Trisomy 21; Trisomy 18; Trisomy 13

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SCREENING
• Blinding Strategy: NONE

Study Groups

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)

Group Type: EXPERIMENTAL

Integrated prenatal screening for Down's syndrome

Intervention Type: OTHER

Analysis of several serum biochemical markers, and fetal nuchal translucency by ultrasound, with computation of an individual risk of fetal aneuploidy.

Serum QUAD Assay for aneuploidy screening

Intervention Type: OTHER

Series of biochemical markers with results integrated into a computational estimate of risk of fetal aneuploidy

Semiconductor MPSS NIPT assay using ccfDNA in maternal blood

Intervention Type: OTHER

Analysis by next-generation sequencing of ccfDNA (circulating cell-free DNA) from maternal blood, using a targeted NIPT assay.

Optical-based MPSS NIPT assay using ccfDNA in maternal blood

Intervention Type: OTHER

Analysis by next-generation sequencing of ccfDNA (circulating cell-free DNA) from maternal blood, using an un-targeted NIPT assay.

Harmony™ Test (Ariosa Diagnostics)

Intervention Type: OTHER

Test that is commercially available (Ariosa Diagnostics). (will be used for benchmarking purposes in a subset of each arm)

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)

Group Type: EXPERIMENTAL

Integrated prenatal screening for Down's syndrome

Intervention Type: OTHER

Analysis of several serum biochemical markers, and fetal nuchal translucency by ultrasound, with computation of an individual risk of fetal aneuploidy.

Serum QUAD Assay for aneuploidy screening

Intervention Type: OTHER

Series of biochemical markers with results integrated into a computational estimate of risk of fetal aneuploidy

Semiconductor MPSS NIPT assay using ccfDNA in maternal blood

Intervention Type: OTHER

Analysis by next-generation sequencing of ccfDNA (circulating cell-free DNA) from maternal blood, using a targeted NIPT assay.

Optical-based MPSS NIPT assay using ccfDNA in maternal blood

Intervention Type: OTHER

Analysis by next-generation sequencing of ccfDNA (circulating cell-free DNA) from maternal blood, using an un-targeted NIPT assay.

Harmony™ Test (Ariosa Diagnostics)

Intervention Type: OTHER

Test that is commercially available (Ariosa Diagnostics). (will be used for benchmarking purposes in a subset of each arm)

Interventions

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.

Intervention Type: OTHER

Serum QUAD Assay for aneuploidy screening

Series of biochemical markers with results integrated into a computational estimate of risk of fetal aneuploidy

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: OTHER

Harmony™ Test (Ariosa Diagnostics)

Test that is commercially available (Ariosa Diagnostics). (will be used for benchmarking purposes in a subset of each arm)

Intervention Type: OTHER

Other Intervention Names

IPS; Prenatal serum screening; Aneuploidy screening; Down's syndrome screening; Downs' syndrome screening; First trimester QUAD prenatal screening assay; NIPD; MPSS; Non-invasive prenatal testing; Non-invasive prenatal diagnosis; NIPD; MPSS; Un-Targeted NIPD; Non-invasive prenatal testing; Non-invasive prenatal diagnosis; DANSR Assay

Eligibility Criteria

Inclusion Criteria

• 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

• 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

• Minimum Eligible Age: 19 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Laval University

OTHER

Sponsor Role: collaborator

Genome Canada

OTHER

Sponsor Role: collaborator

Genome Quebec

OTHER

Sponsor Role: collaborator

Genome British Columbia

INDUSTRY

Sponsor Role: collaborator

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

CHU de Quebec-Universite Laval

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Francois Rousseau, MD MSc FRCPC

Role: PRINCIPAL_INVESTIGATOR

Universite Laval and CHU de Quebec

Sylvie Langlois, MD FRCPC

Role: PRINCIPAL_INVESTIGATOR

University of British Columbia

Locations

Foothills Medical Centre

Calgary, Alberta, Canada

Children's & Women's Health Centre

Vancouver, British Columbia, Canada

The Ottawa Hospital

Ottawa, Ontario, Canada

CHU Ste-Justine

Montreal, Quebec, Canada

CHU de Québec

Québec, Quebec, Canada

Countries

Canada

References

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.

Reference Type: DERIVED

PMID: 34761647 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31231136 (View on PubMed)

Other Identifiers

B13-06-1236

Identifier Type: OTHER

Identifier Source: secondary_id

2014-1236; SIRUL-102531

Identifier Type: -

Identifier Source: org_study_id