Patient case: 56-year-old female with melanoma; genetic feature: KIT (L576P), KIT amplification

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

Summary: The purpose of this study is to provide data and analyses to support 510(k) applications to the FDA for multiple nucleic acid amplification tests (NAATs) diagnostic platforms.

Detailed description: Background & Significance: Infections due to Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) are major threats to public health. In 2008, the World Health Organization (WHO) estimated more than 100 million new worldwide cases for each of NG and CT. In 2013, there were 333,000 NG and 1.4 million CT genitourinary infections in the US. 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. The sensitivity and specificity of commercially available NAATs for the detection of urogenital NG and CT is estimated to be between 90-100%. The CDC also recommends using NAATs for screening and diagnosis of NG and CT in extragenital sites. Due to widespread use and interest in these tests for extragenital NG and CT infections, multiple studies have examined the test characteristics of NAAT tests in comparison to culture and to additional NAAT platforms. For diagnosis of CT, reported sensitivities are 80-100% (pharyngeal) and 46-100% (rectal), with significant variation by platform tested. Reported specificities are >99% for pharyngeal site and 89-100% for the rectum. For diagnosis of NG, reported sensitivities are 72-100% (pharyngeal) and 75-100% (rectal), again with variation by platform. Reported specificities are 72-100% (pharyngeal) and 95-100% (rectal).
  Despite the CDC's recommendations, however, there are currently no FDA-approved commercial NAAT tests for the detection of pharyngeal and rectal NG or CT infections. The FDA's clearance of such assays would increase the ability to diagnose and control NG and CT extragenital infections. This research study will help provide the data required for FDA consideration to clear such assays for marketing.
  Design & Procedures: This will be 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 is being used as a tiebreaker. The performance of the fourth NAAT will not be evaluated. Each manufacturer will provide a specific collection kit and transport media.
  This research study will take place at healthcare clinics which focus on sexually transmitted diseases, women's health, student health, family planning clinics, and clinics specializing in lesbian, gay, bisexual, and transgender (LGBT) health. This research will include specimens collected from 2,500 adult males, females, and transgender persons who are seeking sexually transmitted disease (STD) testing at the participating study clinics. Both symptomatic and asymptomatic subjects will be included in the study population.
  Potential subjects will be identified, assessed for eligibility, and asked to provide oral informed consent. If they agree to take part in the research, study subjects will have eight swabs collected: four pharyngeal and four rectal. The swabs needed for routine clinical care will be taken first. All study procedures will take place during one clinic visit. There will not be a follow-up visit as part of this study. Subjects will continue with routine clinical care as directed by their medical providers.
  Subject participation will be confidential and anonymous. The results of the tests and subject participant in this research will not be placed in the subjects' medical records.
  Each study swab will be used for a specific NAAT, which will be run at one of the two reference testing laboratories. The Anatomic Site Infection Status (ASIS) will be defined by the results of the two other NAATs, and, if necessary, a tiebreaker test. Each anatomic site will be considered in isolation. If fewer than four swabs at a site are completed, that anatomic site (and swab results) will be excluded from the analysis.

Eligibility: Inclusion Criteria:
  1. Attending a participating clinic for evaluation of 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

Relevance to patient case: not relevant