Non-invasive Chromosomal Examination of Trisomy Study

Trisomy 21 Clinical Trial

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Official title:

Non-invasive Chromosomal Examination of Trisomy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01511458
• Other study ID #: TD007
• Status: Completed
• Phase: N/A
• First received: January 13, 2012
• Last updated: July 11, 2014
• Start date: March 2012
• Est. completion date: May 2014

Study information

• Verified date: July 2014
• Source: Ariosa Diagnostics, Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18955
• Est. completion date: May 2014
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 60 Years

Eligibility

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 ß-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.

Study Design

Time Perspective: Prospective

Related Conditions & MeSH terms

• Down Syndrome
• Trisomy 21

Locations

Country	Name	City	State
Belgium	University Hospitals Leuven	Leuven
Canada	Early Risk Assessment Program - University of Alberta	Calgary	Alberta
Canada	Ottawa Hospital and Research Institute	Ottawa	Ontario
Canada	Mount Sinai University	Toronto	Ontario
Canada	University of Toronto	Toronto	Ontario
Italy	University of Perugia	Perugia
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Maastricht University Medical Center	Maastricht
Sweden	Sahlgrenska University Medical Center	Gothenburg
Sweden	Karolinska University Hospital	Stockholm
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	Brigham and Women's Hospital - Center for Fetal Medicine and Prenatal Genetics	Boston	Massachusetts
United States	Duke University Medical Center	Durham	North Carolina
United States	Northshore University Health System	Evanston	Illinois
United States	Fetal Diagnostic Institute of the Pacific	Honolulu	Hawaii
United States	Altus Research	Lake Worth	Florida
United States	Norton Healthcare	Louisville	Kentucky
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Minnesota Perinatal Associates	Minneapolis	Minnesota
United States	Robert Wood Johnson School of Medicine	New Brunswick	New Jersey
United States	St. Peters University Medical Center	New Brunswick	New Jersey
United States	Columbia University	New York	New York
United States	Christiana Care Health System	Newark	Delaware
United States	East Bay Perinatal Associates	Oakland	California
United States	Stanford University	Palo Alto	California
United States	Partners in Obstetrics and Gynecology	Pawtucket	Rhode Island
United States	Thomas Jefferson Univeristy Hospital	Philadelphia	Pennsylvania
United States	Northwest Perinatal Center	Portland	Oregon
United States	Oregon Health Sciences University	Portland	Oregon
United States	Perinatal Diagnostic Center	Riverside	California
United States	University of California San Diego	San Diego	California
United States	California Pacific Medical Center	San Francisco	California
United States	University of California San Francisco	San Francisco	California
United States	The Institute of Prenatal Diagnosis and Reproductive Medicine	San Gabriel	California
United States	Tucson Medical Center	Tucson	Arizona
United States	Women's Health Care Group of Pennsylvania	Wynnewood	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Ariosa Diagnostics, Inc	Perinatal Quality Foundation: Nuchal Translucency Quality Review

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Italy,  Netherlands,  Sweden, 

References & Publications (19)

ACOG Committee on Practice Bulletins. ACOG Practice Bulletin No. 77: screening for fetal chromosomal abnormalities. Obstet Gynecol. 2007 Jan;109(1):217-27. — View Citation

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. — View Citation

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

Borrell A. The ductus venosus in early pregnancy and congenital anomalies. Prenat Diagn. 2004 Sep;24(9):688-92. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in sensitivity and specificity of Ariosa Harmony™ Prenatal Test (AUCt) and combined first-trimester screening for detection of T21.		Enrollment to delivery	No

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