NCT01925742

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
3,819

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Nov 2013

Longer than P75 for not_applicable

Geographic Reach
1 country

5 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 16, 2013

Completed
4 days until next milestone

First Posted

Study publicly available on registry

August 20, 2013

Completed
2 months until next milestone

Study Start

First participant enrolled

November 1, 2013

Completed
3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2017

Completed
Last Updated

February 22, 2018

Status Verified

April 1, 2016

Enrollment Period

3.6 years

First QC Date

August 16, 2013

Last Update Submit

February 21, 2018

Conditions

Trisomy 21Trisomy 18Trisomy 13

Keywords

Fetal aneuploidy

Outcome Measures

Primary Outcomes (1)

  • Number of cases with Fetal trisomy 21, 18 or 13

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

    6 weeks after the delivery date

Secondary Outcomes (1)

  • Number of women with assay failure

    At end of pregnancy.

Other Outcomes (1)

  • Overall costs of screening algorithm

    6 weeks after delivery

Study Arms (2)

Low Risk of aneuploidy

EXPERIMENTAL

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 syndromeOther: Serum QUAD Assay for aneuploidy screeningOther: Semiconductor MPSS NIPT assay using ccfDNA in maternal bloodOther: Optical-based MPSS NIPT assay using ccfDNA in maternal bloodOther: Harmony™ Test (Ariosa Diagnostics)

High risk of aneuploidy

EXPERIMENTAL

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 syndromeOther: Serum QUAD Assay for aneuploidy screeningOther: Semiconductor MPSS NIPT assay using ccfDNA in maternal bloodOther: Optical-based MPSS NIPT assay using ccfDNA in maternal bloodOther: Harmony™ Test (Ariosa Diagnostics)

Interventions

Integrated prenatal screening for Down's syndromeOTHER

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

Also known as: IPS, Prenatal serum screening, Aneuploidy screening, Down's syndrome screening, Downs' syndrome screening
High risk of aneuploidyLow Risk of aneuploidy
Serum QUAD Assay for aneuploidy screeningOTHER

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

Also known as: First trimester QUAD prenatal screening assay
High risk of aneuploidyLow Risk of aneuploidy
Semiconductor MPSS NIPT assay using ccfDNA in maternal bloodOTHER

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

Also known as: NIPD, MPSS, Non-invasive prenatal testing, Non-invasive prenatal diagnosis
High risk of aneuploidyLow Risk of aneuploidy
Optical-based MPSS NIPT assay using ccfDNA in maternal bloodOTHER

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

Also known as: NIPD, MPSS, Un-Targeted NIPD, Non-invasive prenatal testing, Non-invasive prenatal diagnosis
High risk of aneuploidyLow Risk of aneuploidy
Harmony™ Test (Ariosa Diagnostics)OTHER

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

Also known as: DANSR Assay
High risk of aneuploidyLow Risk of aneuploidy

Eligibility Criteria

Age19 Years+
Sexfemale
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)

You may not qualify if:

  • women with multiple gestations
  • women with twin demise (spontaneous or elective) at any gestational age
  • women with active or history of malignancy

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Foothills Medical Centre

Calgary, Alberta, T2N 2T9, Canada

Location

Children's & Women's Health Centre

Vancouver, British Columbia, V6H 3N1, Canada

Location

The Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

CHU Ste-Justine

Montreal, Quebec, H3T 1C5, Canada

Location

CHU de Québec

Québec, Quebec, G1L3L5, Canada

Location

Related Publications (2)

  • 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.

    PMID: 34761647DERIVED

  • 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.

    PMID: 31231136DERIVED

MeSH Terms

Conditions

Down SyndromeTrisomy 18 SyndromeTrisomy 13 Syndrome

Condition Hierarchy (Ancestors)

Intellectual DisabilityNeurobehavioral ManifestationsNeurologic ManifestationsNervous System DiseasesAbnormalities, MultipleCongenital AbnormalitiesCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesChromosome DisordersGenetic Diseases, InbornHeart Defects, CongenitalCardiovascular AbnormalitiesCardiovascular DiseasesHeart Diseases

Study Officials

  • Francois Rousseau, MD MSc FRCPC

    Universite Laval and CHU de Quebec

    PRINCIPAL INVESTIGATOR

  • Sylvie Langlois, MD FRCPC

    University of British Columbia

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
SCREENING
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 16, 2013

First Posted

August 20, 2013

Study Start

November 1, 2013

Primary Completion

June 1, 2017

Study Completion

June 1, 2017

Last Updated

February 22, 2018

Record last verified: 2016-04

Locations

CA(5)