Performance of Nucleic Acid Amplification Tests for the Detection of NG and CT

Sexually Transmitted Infections Clinical Trial

— pNAAT  

Official title:

Performance of Nucleic Acid Amplification Tests for the Detection of Neisseria Gonorrhoeae and Chlamydia Trachomatis in Extragenital Sites

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02870101
• Other study ID #: Pro00073558
• Secondary ID: 5UM1AI104681
• Status: Completed
• Phase: N/A
• Start date: April 10, 2017
• Est. completion date: March 12, 2018

Study information

• Verified date: May 2019
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study was to use participant samples to simultaneously evaluate three nucleic acid amplification tests (NAATs) diagnostic platforms.

Description:

Background & Significance: Infections due to Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) are major threats to public health. Most CT and NG infections are asymptomatic, but infection can lead to serious sequelae, including infertility, chronic pelvic pain, adverse obstetrical outcomes, increased risk of acquiring the human immunodeficiency virus (HIV), and disseminated infection.

There has also been growing concern over antibiotic resistance. In 2013, the US Centers for Disease Control and Prevention (CDC) classified drug-resistant NG as one of the three urgent-level resistant bacteria. Improved detection of extragenital NG is thought to be a crucial component of adequate treatment and for prevention of further resistance.

Currently, the CDC recommends using NAATs to screen and diagnose for NG and CT in the genitourinary tract due to their superior sensitivity compared to traditional culture methods. There are currently no FDA-approved commercial NAAT tests for the detection of pharyngeal and rectal NG or CT infections. The goal of this study is to evaluate the diagnostic performance of three NAAT assays for detection of extragenital NG and CT infections.

Design & Procedures: A cross-sectional, single visit study evaluating the performance of three commercial NAATs to detect NG and CT in the rectum and pharynx. A fourth NAAT will be used as a tiebreaker. The performance of the fourth NAAT will not be evaluated. Each manufacturer will provide a specific swab collection kit and transport media.

This research study will take place at healthcare clinics that focus on sexually transmitted infections, women's health, student health, family planning, and lesbian, gay, bisexual, and transgender (LGBT) health. This research will include specimens collected from adult males, females, and transgender persons seeking sexually transmitted infection (STI) testing at the participating study clinics. Both symptomatic and asymptomatic participants are included in the study population.

Potential participants will be identified, assessed for eligibility, and asked to provide oral informed consent. If a potential participant agrees to take part in the research, the participant will have eight total swabs collected: four swabs from the pharynx and four swabs from the rectum. The swabs needed for routine clinical care are taken first prior to collection of the research study swabs. All study procedures take place during one clinic visit; there are no follow-up visits as part of the study. Participants continue with routine clinical care as directed by their medical providers.

Subject participation is confidential and anonymous. The results of the tests and participation in this research are not placed in the participant's medical records.

Each study swab is used for a specific NAAT and tested at one of the two reference testing laboratories. The Anatomic Site Infection Status (ASIS) is defined by the results of the two other NAATs, and, if necessary, results from the tiebreaker NAAT. Each anatomic site is considered in isolation. If fewer than four swabs at an anatomic site are completed, then the test results from that specific anatomic site are excluded from analysis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2767
• Est. completion date: March 12, 2018
• Est. primary completion date: March 12, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Attending a participating clinic for evaluation of sexually transmitted infections (STIs)

2. =18 years of age at date of screening

3. Able and willing to provide informed consent

4. Willing to comply with study procedures, including collection of 4 swabs each from the pharynx and rectum for NG and CT testing

Exclusion Criteria:

1. Receipt of any systemic antibacterial drug in the past 14 days

2. Receipt of myelosuppressive chemotherapy in the past 30 days

Related Conditions & MeSH terms

• Chlamydia Infections
• Chlamydia Trachomatis Infection
• Communicable Diseases
• Gonorrhea
• Infection
• Neisseria Gonorrhoeae Infection
• Sexually Transmitted Diseases
• Sexually Transmitted Infections

Intervention

Diagnostic Test:
• Nucleic acid amplification test 1 for NG and CT
A combination test using real-time PCR to detect DNA from NG and CT.
• Nucleic acid amplification test 2 for NG and CT
A combination test using target amplification to detect RNA from NG and CT.
• Nucleic acid amplification test 3 for NG and CT
A combination test using real-time PCR to detect DNA from NG and CT.

Locations

Country	Name	City	State
United States	Central Texas Clinical Research	Austin	Texas
United States	Denver Health and Hospital Authority	Denver	Colorado
United States	Wayne State University	Detroit	Michigan
United States	AIDS Health Foundation - Hollywood	Hollywood	California
United States	Los Angeles LGBT Clinic	Los Angeles	California
United States	AIDS Healthcare Foundation - Miami	Miami	Florida
United States	University of Miami	Miami	Florida
United States	Louisiana State University	New Orleans	Louisiana
United States	University of Pittsburgh	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Duke University	National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (22)

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Chernesky MA, Martin DH, Hook EW, Willis D, Jordan J, Wang S, Lane JR, Fuller D, Schachter J. Ability of new APTIMA CT and APTIMA GC assays to detect Chlamydia trachomatis and Neisseria gonorrhoeae in male urine and urethral swabs. J Clin Microbiol. 2005 Jan;43(1):127-31. — View Citation

Cosentino LA, Campbell T, Jett A, Macio I, Zamborsky T, Cranston RD, Hillier SL. Use of nucleic acid amplification testing for diagnosis of anorectal sexually transmitted infections. J Clin Microbiol. 2012 Jun;50(6):2005-8. doi: 10.1128/JCM.00185-12. Epub 2012 Apr 4. — View Citation

Deguchi T, Yasuda M, Ito S. Management of pharyngeal gonorrhea is crucial to prevent the emergence and spread of antibiotic-resistant Neisseria gonorrhoeae. Antimicrob Agents Chemother. 2012 Jul;56(7):4039-40; author re[ply 4041-2. doi: 10.1128/AAC.00505-12. — View Citation

Geelen TH, Rossen JW, Beerens AM, Poort L, Morré SA, Ritmeester WS, van Kruchten HE, van de Pas MM, Savelkoul PH. Performance of cobas® 4800 and m2000 real-time™ assays for detection of Chlamydia trachomatis and Neisseria gonorrhoeae in rectal and self-collected vaginal specimen. Diagn Microbiol Infect Dis. 2013 Oct;77(2):101-5. doi: 10.1016/j.diagmicrobio.2013.06.020. Epub 2013 Jul 23. — View Citation

Goldenberg SD, Finn J, Sedudzi E, White JA, Tong CY. Performance of the GeneXpert CT/NG assay compared to that of the Aptima AC2 assay for detection of rectal Chlamydia trachomatis and Neisseria gonorrhoeae by use of residual Aptima Samples. J Clin Microbiol. 2012 Dec;50(12):3867-9. doi: 10.1128/JCM.01930-12. Epub 2012 Sep 19. — View Citation

Harryman L, Scofield S, Macleod J, Carrington D, Williams OM, Fernandes A, Horner P. Comparative performance of culture using swabs transported in Amies medium and the Aptima Combo 2 nucleic acid amplification test in detection of Neisseria gonorrhoeae from genital and extra-genital sites: a retrospective study. Sex Transm Infect. 2012 Feb;88(1):27-31. doi: 10.1136/sextrans-2011-050075. Epub 2011 Oct 27. — View Citation

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Moncada J, Schachter J, Liska S, Shayevich C, Klausner JD. Evaluation of self-collected glans and rectal swabs from men who have sex with men for detection of Chlamydia trachomatis and Neisseria gonorrhoeae by use of nucleic acid amplification tests. J Clin Microbiol. 2009 Jun;47(6):1657-62. doi: 10.1128/JCM.02269-08. Epub 2009 Apr 15. — View Citation

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Ota KV, Tamari IE, Smieja M, Jamieson F, Jones KE, Towns L, Juzkiw J, Richardson SE. Detection of Neisseria gonorrhoeae and Chlamydia trachomatis in pharyngeal and rectal specimens using the BD Probetec ET system, the Gen-Probe Aptima Combo 2 assay and culture. Sex Transm Infect. 2009 Jun;85(3):182-6. doi: 10.1136/sti.2008.034140. Epub 2009 Jan 6. — View Citation

Perry MD, Jones RN, Corden SA. Is confirmatory testing of Roche cobas 4800 CT/NG test Neisseria gonorrhoeae positive samples required? Comparison of the Roche cobas 4800 CT/NG test with an opa/pap duplex assay for the detection of N gonorrhoeae. Sex Transm Infect. 2014 Jun;90(4):303-8. doi: 10.1136/sextrans-2013-051410. Epub 2014 Mar 20. — View Citation

Pope CF, Hay P, Alexander S, Capaldi K, Dave J, Sadiq ST, Ison CA, Planche T. Positive predictive value of the Becton Dickinson VIPER system and the ProbeTec GC Q x assay, in extracted mode, for detection of Neisseria gonorrhoeae. Sex Transm Infect. 2010 Nov;86(6):465-9. doi: 10.1136/sti.2010.044065. — View Citation

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Schachter J, Moncada J, Liska S, Shayevich C, Klausner JD. Nucleic acid amplification tests in the diagnosis of chlamydial and gonococcal infections of the oropharynx and rectum in men who have sex with men. Sex Transm Dis. 2008 Jul;35(7):637-42. doi: 10.1097/OLQ.0b013e31817bdd7e. — View Citation

Tabrizi SN, Unemo M, Limnios AE, Hogan TR, Hjelmevoll SO, Garland SM, Tapsall J. Evaluation of six commercial nucleic acid amplification tests for detection of Neisseria gonorrhoeae and other Neisseria species. J Clin Microbiol. 2011 Oct;49(10):3610-5. doi: 10.1128/JCM.01217-11. Epub 2011 Aug 3. — View Citation

Trebach JD, Chaulk CP, Page KR, Tuddenham S, Ghanem KG. Neisseria gonorrhoeae and Chlamydia trachomatis among women reporting extragenital exposures. Sex Transm Dis. 2015 May;42(5):233-9. doi: 10.1097/OLQ.0000000000000248. — View Citation

Weström L, Joesoef R, Reynolds G, Hagdu A, Thompson SE. Pelvic inflammatory disease and fertility. A cohort study of 1,844 women with laparoscopically verified disease and 657 control women with normal laparoscopic results. Sex Transm Dis. 1992 Jul-Aug;19(4):185-92. — View Citation

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* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Nucleic Acid Amplification Test (NAAT) 1 Index Test Results Relative to Anatomic Site Infection Status (ASIS) Reference Results for Neisseria Gonorrhoeae (NG) in Pharynx	NAAT 1 index test results include negative, positive, and no result. ASIS reference results are the combination of the NAAT 2 and NAAT 3 index test results. ASIS reference results include negative, positive, indeterminate, and invalid.	One day
Primary	Number of Participants With Nucleic Acid Amplification Test (NAAT) 1 Index Test Results Relative to Anatomic Site Infection Status (ASIS) Reference Results for Neisseria Gonorrhoeae (NG) in Rectum	NAAT 1 index test results include negative, positive, and no result. ASIS reference results are the combination of the NAAT 2 and NAAT 3 index test results. ASIS reference results include negative, positive, indeterminate, and invalid.	One day
Primary	Number of Participants With Nucleic Acid Amplification Test (NAAT) 2 Index Test Results Relative to Anatomic Site Infection Status (ASIS) Reference Results for Neisseria Gonorrhoeae (NG) in Pharynx	NAAT 2 index test results include negative, positive, equivocal, and no result. ASIS reference results are the combination of the NAAT 1 and NAAT 3 index test results. ASIS reference results include negative, positive, indeterminate, and invalid	One day
Primary	Number of Participants With Nucleic Acid Amplification Test (NAAT) 2 Index Test Results Relative to Anatomic Site Infection Status (ASIS) Reference Results for Neisseria Gonorrhoeae (NG) in Rectum	NAAT 2 index test results include negative, positive, equivocal, and no result. ASIS reference results are the combination of the NAAT 1 and NAAT 3 index test results. ASIS reference results include negative, positive, indeterminate, and invalid.	One day
Primary	Number of Participants With Nucleic Acid Amplification Test (NAAT) 3 Index Test Results Relative to Anatomic Site Infection Status (ASIS) Reference Results for Neisseria Gonorrhoeae (NG) in Pharynx	NAAT 3 index test results include negative, positive, and no result. ASIS reference results are the combination of the NAAT 1 and NAAT 2 index test results. ASIS reference results include negative, positive, indeterminate, and invalid.	One day
Primary	Number of Participants With Nucleic Acid Amplification Test (NAAT) 3 Index Test Results Relative to Anatomic Site Infection Status (ASIS) Reference Results for Neisseria Gonorrhoeae (NG) in Rectum	NAAT 3 index test results include negative, positive, and no result. ASIS reference results are the combination of the NAAT 1 and NAAT 2 index test results. ASIS reference results include negative, positive, indeterminate, and invalid.	One day
Primary	Number of Participants With Nucleic Acid Amplification Test (NAAT) 1 Index Test Results Relative to Anatomic Site Infection Status (ASIS) Reference Results for Chlamydia Trachomatis (CT) in Pharynx	NAAT 1 index test results include negative, positive, and no result. ASIS reference results are the combination of the NAAT 2 and NAAT 3 index test results. ASIS reference results include negative, positive, indeterminate, and invalid.	One day
Primary	Number of Participants With Nucleic Acid Amplification Test (NAAT) 1 Index Test Results Relative to Anatomic Site Infection Status (ASIS) Reference Results for Chlamydia Trachomatis (CT) in Rectum	NAAT 1 index test results include negative, positive, and no result. ASIS reference results are the combination of the NAAT 2 and NAAT 3 index test results. ASIS reference results include negative, positive, indeterminate, and invalid.	One day
Primary	Number of Participants With Nucleic Acid Amplification Test (NAAT) 2 Index Test Results Relative to Anatomic Site Infection Status (ASIS) Reference Results for Chlamydia Trachomatis (CT) in Pharynx	NAAT 2 index test results include negative, positive, equivocal, and no result. ASIS reference results are the combination of the NAAT 1 and NAAT 3 index test results. ASIS reference results include negative, positive, indeterminate, and invalid.	One day
Primary	Number of Participants With Nucleic Acid Amplification Test (NAAT) 2 Index Test Results Relative to Anatomic Site Infection Status (ASIS) Reference Results for Chlamydia Trachomatis (CT) in Rectum	NAAT 2 index test results include negative, positive, equivocal, and no result. ASIS reference results are the combination of the NAAT 1 and NAAT 3 index test results. ASIS reference results include negative, positive, indeterminate, and invalid.	One day
Primary	Number of Participants With Nucleic Acid Amplification Test (NAAT) 3 Index Test Results Relative to Anatomic Site Infection Status (ASIS) Reference Results for Chlamydia Trachomatis (CT) in Pharynx	NAAT 3 index test results include negative, positive, equivocal, and no result. ASIS reference results are the combination of the NAAT 1 and NAAT 2 index test results. ASIS reference results include negative, positive, indeterminate, and invalid.	One day
Primary	Number of Participants With Nucleic Acid Amplification Test (NAAT) 3 Index Test Results Relative to Anatomic Site Infection Status (ASIS) Reference Results for Chlamydia Trachomatis (CT) in Rectum	NAAT 3 index test results include negative, positive, equivocal, and no result. ASIS reference results are the combination of the NAAT 1 and NAAT 2 index test results. ASIS reference results include negative, positive, indeterminate, and invalid.	One day