Trisomy 21NEXTNCT01511458
Non-invasive Chromosomal Examination of Trisomy Study
An observational study of Trisomy 21, run by Roche Sequencing Solutions at 36 sites in 6 countries.
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)… Read more about this study
- Who is it for?
- Ages 18 to 60 years, women only
- Conditions the study is for
- Trisomy 21
- How many people
- 18,955 participants
- Where
- 36 sitesin 6 countries
- Study dates
- Mar 2012to May 2014
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- Women only
- No healthy volunteers
- Adult
Study population: Pregnant women presenting for combined first trimester screening as part of routine prenatal care
Who may be able to join
- Subject is at least 18 years old and can provide informed consent.
- Subject is planning a hospital delivery.
- 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.
- 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.
Who cannot join
- Subject has known aneuploidy.
- Subject has active or history of malignancy requiring major surgery and/or systemic chemotherapy.
- 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.
Trial locations and contacts
36 sites in 6 countries.
36 sites in 6 countries
United States26 sites
Abington Memorial Hospital
Abington, Pennsylvania, 19001
Brigham and Women's Hospital - Center for Fetal Medicine and Prenatal Genetics
Boston, Massachusetts, 02115
Duke University Medical Center
Durham, North Carolina, 27710
Northshore University Health System
Evanston, Illinois, 60201
Fetal Diagnostic Institute of the Pacific
Honolulu, Hawaii, 96814
Altus Research
Lake Worth, Florida, 33461
Norton Healthcare
Louisville, Kentucky, 40202
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Minnesota Perinatal Associates
Minneapolis, Minnesota, 55407
Robert Wood Johnson School of Medicine
New Brunswick, New Jersey, 08901
St. Peters University Medical Center
New Brunswick, New Jersey, 08901
Columbia University
New York, New York, 10032
Christiana Care Health System
Newark, Delaware, 19718
East Bay Perinatal Associates
Oakland, California, 94609
Stanford University
Palo Alto, California, 94305-5317
Partners in Obstetrics and Gynecology
Pawtucket, Rhode Island, 02860
Thomas Jefferson Univeristy Hospital
Philadelphia, Pennsylvania, 19107
Northwest Perinatal Center
Portland, Oregon, 97225
Oregon Health Sciences University
Portland, Oregon, 97239
Perinatal Diagnostic Center
Riverside, California, 92501
University of California San Diego
San Diego, California, 92037-1300
California Pacific Medical Center
San Francisco, California, 94118
University of California San Francisco
San Francisco, California, 94143
The Institute of Prenatal Diagnosis and Reproductive Medicine
San Gabriel, California, 91776
Tucson Medical Center
Tucson, Arizona, 85712
Women's Health Care Group of Pennsylvania
Wynnewood, Pennsylvania, 19096
Canada4 sites
Early Risk Assessment Program - University of Alberta
Calgary, Alberta, T2N 4N1
Ottawa Hospital and Research Institute
Ottawa, Ontario, ON1Kh8L6
Mount Sinai University
Toronto, Ontario, M5G 1X5
University of Toronto
Toronto, Ontario, M5G1X8
Netherlands2 sites
Leiden University Medical Center
Leiden, 2333
Maastricht University Medical Center
Maastricht, 6202
Sweden2 sites
Sahlgrenska University Medical Center
Gothenburg, SE-41685
Karolinska University Hospital
Stockholm, 14186
About this study
Official title: Non-invasive Chromosomal Examination of Trisomy
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.
- Conditions
- Trisomy 21
- Keywords
- Pregnancy, Fetal aneuploidy, Trisomy 21, Down Syndrome, Prenatal screening, Non-invasive prenatal testing, First trimester, Combined screening, Nuchal translucency, PAPP-A, hCG, cell free DNA, cf DNA, DNA, Performance characteristics of non-invasive first trimester screening, Harmony Prenatal Test
- Medical subject headings
- Down Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Case | Patient with a trisomy 21 pregnancy confirmed by genetic testing. | |
| Control | Patients without a trisomy 21 pregnancy confirmed by either genetic testing or a normal newborn phenotype. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in sensitivity and specificity of Ariosa Harmony™ Prenatal Test (AUCt) and combined first-trimester screening for detection of T21.
Measured: Enrollment to delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2012 (estimated)
- Study startMar 2012
- Primary completionNov 2013
- Study completionMay 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (20)Papers the sponsor has linked to this study.
- Other trials for Trisomy 21Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Time perspective
- Prospective
- Enrolment
- 18,955 participants (actual)
Sponsor and investigators
- Lead sponsor
- Roche Sequencing Solutions
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Perinatal Quality Foundation: Nuchal Translucency Quality Review
- Responsible party
- Sponsor
- Investigators
- Mary E. Norton, MD, Principal investigator, Stanford UniversityRonald Wapner, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01511458
- Sponsor's protocol ID
- TD007
- Acronym
- NEXT
- Status last verified
- Jul 2014
- First submitted
- 13 Jan 2012
- Last updated
- 14 Jul 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
American College of Obstetricians and Gynecologists. Guidelines for Perinatal Care, Sixth Edition, October 2007.
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.
PubMed 21210474Malone 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.
PubMed 16282175Nicolaides 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.
PubMed 15736186Cicero 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.
PubMed 15027007Borrell A. The ductus venosus in early pregnancy and congenital anomalies. Prenat Diagn. 2004 Sep;24(9):688-92. doi: 10.1002/pd.958.
PubMed 15386454Faiola 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.
PubMed 15937972Sonek 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.
PubMed 17346551ACOG 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.
PubMed 17197615American 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.
PubMed 18055749Ehrich 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.
PubMed 21310373Lo 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.
PubMed 9274585Fan 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.
PubMed 18838674Chiu 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.
PubMed 19073917Chiu 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.
PubMed 20026875
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-invasive Chromosomal Examination of Trisomy
- ClinicalTrials.gov ID
- NCT01511458
- Acronym / sponsor ID
- NEXT / TD007
- Conditions
- Trisomy 21
- Keywords
- Pregnancy, Fetal aneuploidy, Trisomy 21, Down Syndrome, Prenatal screening, Non-invasive prenatal testing, First trimester, Combined screening
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 18,955 participants (actual)
- Lead sponsor
- Roche Sequencing SolutionsIndustry (pharma, biotech, devices)
- Collaborators
- Perinatal Quality Foundation: Nuchal Translucency Quality Review
- Study start
- Mar 2012
- Primary completion
- Nov 2013 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 18 Jan 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Case | – | –Patient with a trisomy 21 pregnancy confirmed by genetic testing. |
| Control | – | –Patients without a trisomy 21 pregnancy confirmed by either genetic testing or a normal newborn phenotype. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- Pregnant women presenting for combined first trimester screening as part of routine prenatal care
Key inclusion criteria (4 listed)
- Subject is at least 18 years old and can provide informed consent.
- Subject is planning a hospital delivery.
- 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.
- 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.
Key exclusion criteria (3 listed)
- Subject has known aneuploidy.
- Subject has active or history of malignancy requiring major surgery and/or systemic chemotherapy.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Difference in sensitivity and specificity of Ariosa Harmony™ Prenatal Test (AUCt) and combined first-trimester screening for detection of T21.
Time frame: Enrollment to delivery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2014.
- BackgroundAmerican College of Obstetricians and Gynecologists. Guidelines for Perinatal Care, Sixth Edition, October 2007.
- Background: PubMed 21210474Nicolaides 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.
- Background: PubMed 16282175Malone 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.
- Background: PubMed 15736186Nicolaides 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.
- Background: PubMed 15027007Cicero 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.
- Background: PubMed 15386454Borrell A. The ductus venosus in early pregnancy and congenital anomalies. Prenat Diagn. 2004 Sep;24(9):688-92. doi: 10.1002/pd.958.
- Background: PubMed 15937972Faiola 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.
- Background: PubMed 17346551Sonek 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.
- Background: PubMed 17197615ACOG 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.
- Background: PubMed 18055749American 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.
- Background: PubMed 21310373Ehrich 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.
- Background: PubMed 9274585Lo 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.
- Click here for more information about Ariosa DiagnosticsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mary E. Norton, MD principal investigator
Stanford University
Ronald Wapner, MD principal investigator
Columbia University
36 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Trisomy 21, run by Roche Sequencing Solutions at 36 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 36 sites in United States, Canada, Netherlands, Sweden, Belgium and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in sensitivity and specificity of Ariosa Harmony™ Prenatal Test (AUCt) and combined first-trimester screening for detection of T21. (time frame: Enrollment to delivery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01511458, which also lists 20 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2014.