Non-invasive Chromosomal Examination of Trisomy Study

NCT ID: NCT01511458

Last Updated: 2014-07-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

18955 participants

Study Classification

OBSERVATIONAL

Study Start Date

2012-03-31

Study Completion Date

2014-05-31

Brief Summary

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The purpose of this blinded, multi-center, prospective, case-controlled study is to compare the Ariosa Harmony™ Prenatal Test for trisomy 21 detection with a standard first-trimester prenatal screening test consisting of serum screening (PAPP-A,free beta-hCG \[β-hCG\] or total hCG) and a nuchal translucency (NT) measurement (i.e. combined first trimester screening) in a general screened population.

The performance characteristics of these two test modalities will be assessed relative to the clinical reference standard of genetic analysis of the fetus or phenotypic characterization and genetic analysis of the newborn.

Detailed Description

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Conditions

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Trisomy 21

Study Design

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Study Time Perspective

PROSPECTIVE

Study Groups

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Case

Patient with a trisomy 21 pregnancy confirmed by genetic testing.

No interventions assigned to this group

Control

Patients without a trisomy 21 pregnancy confirmed by either genetic testing or a normal newborn phenotype.

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

1. Subject is at least 18 years old and can provide informed consent.
2. Subject is planning a hospital delivery.
3. Subject has a singleton pregnancy with a documented gestational age between 10 weeks, 0 days, and 14 weeks, 2 days, inclusive, at the time of the study blood sample collection.
4. Subject is planning to undergo combined first trimester prenatal screening that includes NT measurement, and when indicated, serum screening with total or free β-hCG and PAPP-A.

Exclusion Criteria

1. Subject has known aneuploidy.
2. Subject has active or history of malignancy requiring major surgery and/or systemic chemotherapy.
3. Subject has a twin demise at any gestational age. Twin demise includes any reductions, spontaneous or elective, after sonographic identification of a second (or more) gestational sac. Any clinical, sonographic, or other testing that suggests twin demise would serve as an exclusion criterion.
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Perinatal Quality Foundation: Nuchal Translucency Quality Review

UNKNOWN

Sponsor Role collaborator

Roche Sequencing Solutions

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mary E. Norton, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Ronald Wapner, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

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Tucson Medical Center

Tucson, Arizona, United States

Site Status

East Bay Perinatal Associates

Oakland, California, United States

Site Status

Stanford University

Palo Alto, California, United States

Site Status

Perinatal Diagnostic Center

Riverside, California, United States

Site Status

University of California San Diego

San Diego, California, United States

Site Status

California Pacific Medical Center

San Francisco, California, United States

Site Status

University of California San Francisco

San Francisco, California, United States

Site Status

The Institute of Prenatal Diagnosis and Reproductive Medicine

San Gabriel, California, United States

Site Status

Christiana Care Health System

Newark, Delaware, United States

Site Status

Altus Research

Lake Worth, Florida, United States

Site Status

Fetal Diagnostic Institute of the Pacific

Honolulu, Hawaii, United States

Site Status

Northshore University Health System

Evanston, Illinois, United States

Site Status

Norton Healthcare

Louisville, Kentucky, United States

Site Status

Brigham and Women's Hospital - Center for Fetal Medicine and Prenatal Genetics

Boston, Massachusetts, United States

Site Status

Minnesota Perinatal Associates

Minneapolis, Minnesota, United States

Site Status

Robert Wood Johnson School of Medicine

New Brunswick, New Jersey, United States

Site Status

St. Peters University Medical Center

New Brunswick, New Jersey, United States

Site Status

Columbia University

New York, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Northwest Perinatal Center

Portland, Oregon, United States

Site Status

Oregon Health Sciences University

Portland, Oregon, United States

Site Status

Abington Memorial Hospital

Abington, Pennsylvania, United States

Site Status

Thomas Jefferson Univeristy Hospital

Philadelphia, Pennsylvania, United States

Site Status

Women's Health Care Group of Pennsylvania

Wynnewood, Pennsylvania, United States

Site Status

Partners in Obstetrics and Gynecology

Pawtucket, Rhode Island, United States

Site Status

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

University Hospitals Leuven

Leuven, , Belgium

Site Status

Early Risk Assessment Program - University of Alberta

Calgary, Alberta, Canada

Site Status

Ottawa Hospital and Research Institute

Ottawa, Ontario, Canada

Site Status

Mount Sinai University

Toronto, Ontario, Canada

Site Status

University of Toronto

Toronto, Ontario, Canada

Site Status

University of Perugia

Perugia, , Italy

Site Status

Leiden University Medical Center

Leiden, , Netherlands

Site Status

Maastricht University Medical Center

Maastricht, , Netherlands

Site Status

Sahlgrenska University Medical Center

Gothenburg, , Sweden

Site Status

Karolinska University Hospital

Stockholm, , Sweden

Site Status

Countries

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United States Belgium Canada Italy Netherlands Sweden

References

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American College of Obstetricians and Gynecologists. Guidelines for Perinatal Care, Sixth Edition, October 2007.

Reference Type BACKGROUND

Nicolaides KH. A model for a new pyramid of prenatal care based on the 11 to 13 weeks' assessment. Prenat Diagn. 2011 Jan;31(1):3-6. doi: 10.1002/pd.2685. No abstract available.

Reference Type BACKGROUND
PMID: 21210474 (View on PubMed)

Malone FD, Canick JA, Ball RH, Nyberg DA, Comstock CH, Bukowski R, Berkowitz RL, Gross SJ, Dugoff L, Craigo SD, Timor-Tritsch IE, Carr SR, Wolfe HM, Dukes K, Bianchi DW, Rudnicka AR, Hackshaw AK, Lambert-Messerlian G, Wald NJ, D'Alton ME; First- and Second-Trimester Evaluation of Risk (FASTER) Research Consortium. First-trimester or second-trimester screening, or both, for Down's syndrome. N Engl J Med. 2005 Nov 10;353(19):2001-11. doi: 10.1056/NEJMoa043693.

Reference Type BACKGROUND
PMID: 16282175 (View on PubMed)

Nicolaides KH, Spencer K, Avgidou K, Faiola S, Falcon O. Multicenter study of first-trimester screening for trisomy 21 in 75 821 pregnancies: results and estimation of the potential impact of individual risk-orientated two-stage first-trimester screening. Ultrasound Obstet Gynecol. 2005 Mar;25(3):221-6. doi: 10.1002/uog.1860.

Reference Type BACKGROUND
PMID: 15736186 (View on PubMed)

Cicero S, Rembouskos G, Vandecruys H, Hogg M, Nicolaides KH. Likelihood ratio for trisomy 21 in fetuses with absent nasal bone at the 11-14-week scan. Ultrasound Obstet Gynecol. 2004 Mar;23(3):218-23. doi: 10.1002/uog.992.

Reference Type BACKGROUND
PMID: 15027007 (View on PubMed)

Borrell A. The ductus venosus in early pregnancy and congenital anomalies. Prenat Diagn. 2004 Sep;24(9):688-92. doi: 10.1002/pd.958.

Reference Type BACKGROUND
PMID: 15386454 (View on PubMed)

Faiola S, Tsoi E, Huggon IC, Allan LD, Nicolaides KH. Likelihood ratio for trisomy 21 in fetuses with tricuspid regurgitation at the 11 to 13 + 6-week scan. Ultrasound Obstet Gynecol. 2005 Jul;26(1):22-7. doi: 10.1002/uog.1922.

Reference Type BACKGROUND
PMID: 15937972 (View on PubMed)

Sonek J, Borenstein M, Dagklis T, Persico N, Nicolaides KH. Frontomaxillary facial angle in fetuses with trisomy 21 at 11-13(6) weeks. Am J Obstet Gynecol. 2007 Mar;196(3):271.e1-4. doi: 10.1016/j.ajog.2006.10.891.

Reference Type BACKGROUND
PMID: 17346551 (View on PubMed)

ACOG Committee on Practice Bulletins. ACOG Practice Bulletin No. 77: screening for fetal chromosomal abnormalities. Obstet Gynecol. 2007 Jan;109(1):217-27. doi: 10.1097/00006250-200701000-00054.

Reference Type BACKGROUND
PMID: 17197615 (View on PubMed)

American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 88, December 2007. Invasive prenatal testing for aneuploidy. Obstet Gynecol. 2007 Dec;110(6):1459-67. doi: 10.1097/01.AOG.0000291570.63450.44.

Reference Type BACKGROUND
PMID: 18055749 (View on PubMed)

Ehrich M, Deciu C, Zwiefelhofer T, Tynan JA, Cagasan L, Tim R, Lu V, McCullough R, McCarthy E, Nygren AO, Dean J, Tang L, Hutchison D, Lu T, Wang H, Angkachatchai V, Oeth P, Cantor CR, Bombard A, van den Boom D. Noninvasive detection of fetal trisomy 21 by sequencing of DNA in maternal blood: a study in a clinical setting. Am J Obstet Gynecol. 2011 Mar;204(3):205.e1-11. doi: 10.1016/j.ajog.2010.12.060. Epub 2011 Feb 18.

Reference Type BACKGROUND
PMID: 21310373 (View on PubMed)

Lo YM, Corbetta N, Chamberlain PF, Rai V, Sargent IL, Redman CW, Wainscoat JS. Presence of fetal DNA in maternal plasma and serum. Lancet. 1997 Aug 16;350(9076):485-7. doi: 10.1016/S0140-6736(97)02174-0.

Reference Type BACKGROUND
PMID: 9274585 (View on PubMed)

Fan HC, Blumenfeld YJ, Chitkara U, Hudgins L, Quake SR. Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood. Proc Natl Acad Sci U S A. 2008 Oct 21;105(42):16266-71. doi: 10.1073/pnas.0808319105. Epub 2008 Oct 6.

Reference Type BACKGROUND
PMID: 18838674 (View on PubMed)

Chiu RW, Chan KC, Gao Y, Lau VY, Zheng W, Leung TY, Foo CH, Xie B, Tsui NB, Lun FM, Zee BC, Lau TK, Cantor CR, Lo YM. Noninvasive prenatal diagnosis of fetal chromosomal aneuploidy by massively parallel genomic sequencing of DNA in maternal plasma. Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20458-63. doi: 10.1073/pnas.0810641105. Epub 2008 Dec 10.

Reference Type BACKGROUND
PMID: 19073917 (View on PubMed)

Chiu RW, Sun H, Akolekar R, Clouser C, Lee C, McKernan K, Zhou D, Nicolaides KH, Lo YM. Maternal plasma DNA analysis with massively parallel sequencing by ligation for noninvasive prenatal diagnosis of trisomy 21. Clin Chem. 2010 Mar;56(3):459-63. doi: 10.1373/clinchem.2009.136507. Epub 2009 Dec 21.

Reference Type BACKGROUND
PMID: 20026875 (View on PubMed)

Palomaki GE, Kloza EM, Lambert-Messerlian GM, Haddow JE, Neveux LM, Ehrich M, van den Boom D, Bombard AT, Deciu C, Grody WW, Nelson SF, Canick JA. DNA sequencing of maternal plasma to detect Down syndrome: an international clinical validation study. Genet Med. 2011 Nov;13(11):913-20. doi: 10.1097/GIM.0b013e3182368a0e.

Reference Type BACKGROUND
PMID: 22005709 (View on PubMed)

Dhallan R, Guo X, Emche S, Damewood M, Bayliss P, Cronin M, Barry J, Betz J, Franz K, Gold K, Vallecillo B, Varney J. A non-invasive test for prenatal diagnosis based on fetal DNA present in maternal blood: a preliminary study. Lancet. 2007 Feb 10;369(9560):474-81. doi: 10.1016/S0140-6736(07)60115-9.

Reference Type BACKGROUND
PMID: 17292767 (View on PubMed)

Tong YK, Jin S, Chiu RW, Ding C, Chan KC, Leung TY, Yu L, Lau TK, Lo YM. Noninvasive prenatal detection of trisomy 21 by an epigenetic-genetic chromosome-dosage approach. Clin Chem. 2010 Jan;56(1):90-8. doi: 10.1373/clinchem.2009.134114. Epub 2009 Oct 22.

Reference Type BACKGROUND
PMID: 19850629 (View on PubMed)

Ghanta S, Mitchell ME, Ames M, Hidestrand M, Simpson P, Goetsch M, Thilly WG, Struble CA, Tomita-Mitchell A. Non-invasive prenatal detection of trisomy 21 using tandem single nucleotide polymorphisms. PLoS One. 2010 Oct 8;5(10):e13184. doi: 10.1371/journal.pone.0013184.

Reference Type BACKGROUND
PMID: 20949031 (View on PubMed)

Norton ME, Jacobsson B, Swamy GK, Laurent LC, Ranzini AC, Brar H, Tomlinson MW, Pereira L, Spitz JL, Hollemon D, Cuckle H, Musci TJ, Wapner RJ. Cell-free DNA analysis for noninvasive examination of trisomy. N Engl J Med. 2015 Apr 23;372(17):1589-97. doi: 10.1056/NEJMoa1407349. Epub 2015 Apr 1.

Reference Type DERIVED
PMID: 25830321 (View on PubMed)

Related Links

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http://www.ariosadx.com

Click here for more information about Ariosa Diagnostics

Other Identifiers

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TD007

Identifier Type: -

Identifier Source: org_study_id

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