Diagnostic Tests for Syphilis in Pregnancy

Recruiting at 8 trial locations

Overseen By Irene Stafford, MD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: The University of Texas Health Science Center, Houston

Disqualifiers: False positive, Moving outside study

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 96

924 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate how well two different tests detect syphilis, a sexually transmitted infection, in pregnant individuals and newborns. Researchers will use qPCR (Quantitative polymerase chain reaction assay) and TMA (Aptima Treponema pallidum transcription-mediated amplification assay) to identify the bacteria causing syphilis. The goal is to improve diagnosis by using these tests on samples from individuals diagnosed with syphilis according to standard guidelines. The trial seeks pregnant individuals diagnosed with syphilis at 12 weeks or more into their pregnancy, as well as newborns affected by syphilis within 72 hours of birth. As an unphased trial, this study offers a unique opportunity to advance diagnostic methods for syphilis, potentially benefiting future patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It focuses on testing for syphilis, so it's best to ask the study team for guidance.

What prior data suggests that these diagnostic tests are safe for use in pregnancy?

Previous studies have shown that both the Aptima Treponema pallidum TMA test and the qPCR test are safe, with no major safety concerns reported. These tests detect the bacteria that cause syphilis. The Aptima TMA test accurately identifies individuals with the infection by detecting the bacteria's genetic material. The qPCR test finds and measures the bacteria's DNA, ensuring precise detection.

As diagnostic tests, their primary purpose is to identify syphilis without directly affecting the body. Participation in a study using these tests is generally considered safe, as they do not alter bodily functions. Instead, they provide a clear diagnosis, presenting minimal risk for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the new diagnostic tests for syphilis in pregnancy because they offer a more precise and potentially faster way to detect the infection. Unlike traditional blood tests that look for antibodies, the Aptima TMA assay and qPCR assay directly detect the DNA of Treponema pallidum, the bacteria causing syphilis. This direct detection might lead to earlier and more accurate diagnosis, which is crucial for preventing complications in pregnancy. By aligning with CDC guidelines, these molecular tests could greatly improve the standard of care for expectant mothers and their babies.

What evidence suggests that these diagnostic tests are effective for detecting syphilis in pregnancy?

Research has shown that the Aptima Treponema pallidum TMA test effectively detects the bacteria causing syphilis, aiding in identifying cases and potentially preventing the infection's spread. Studies indicate that the qPCR test is 94.7% effective in detecting early syphilis cases and has consistently matched syphilis diagnoses across various settings. This trial will evaluate both the Aptima TMA assay and the qPCR test as promising methods to enhance syphilis detection, particularly in pregnant individuals, helping to prevent complications for both mothers and babies. ^{1 2 3 6 7}

Who Is on the Research Team?

Irene Stafford, MD

Principal Investigator

The University of Texas Health Science Center, Houston

Are You a Good Fit for This Trial?

This trial is for newborns up to 72 hours old from pregnancies impacted by syphilis and mothers diagnosed with syphilis per CDC guidelines, treated or not. It includes pregnant women at least 12 weeks along or within 96 hours postpartum. Those planning to move away before testing ends or without a true syphilis diagnosis are excluded.

Inclusion Criteria

My newborn was exposed to syphilis and is under 72 hours old.

I have been diagnosed with syphilis during my pregnancy or within 96 hours after giving birth.

Exclusion Criteria

Planning to move outside of study prior to ND testing

If you are pregnant or a newborn and do not have a specific condition called syphilis (which can sometimes give a false positive result), you will not be eligible.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Molecular Testing

Evaluation of diagnostic molecular techniques (qPCR and TMA) for detecting Treponema pallidum in maternal and neonatal specimens

From birth up to 96 hours after birth

Multiple sample collections within 96 hours post-birth

Follow-up

Participants are monitored for safety and effectiveness after testing, with clinical data collected as part of standard care

18 months

What Are the Treatments Tested in This Trial?

Interventions

• Aptima Treponema pallidum transcription-mediated amplification (TMA) assay for detection of Treponema pallidum
• Quantitative polymerase chain reaction (qPCR) assay for detection of Treponema pallidum

Trial Overview The study tests two molecular diagnostic techniques, qPCR and TMA, for detecting the bacterium causing syphilis in maternal and neonatal specimens. These methods are compared against the CDC's STI Treatment Guidelines for diagnosing adult and congenital syphilis.

How Is the Trial Designed?

Group I: Molecular testing for detection of T. pallidum and use of CDC guidelines for diagnosis of syphilis Experimental Treatment 3 Interventions

Aptima Treponema pallidum transcription-mediated amplification (TMA) assay for detection of Treponema pallidum is already approved in United States, European Union for the following indications:

Approved in United States as Aptima TMA assay for:

• Detection of Treponema pallidum in maternal and neonatal specimens

Approved in European Union as Aptima TMA assay for:

• Detection of Treponema pallidum in maternal and neonatal specimens

Who Is Running the Clinical Trial?

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Published Research Related to This Trial

In a study of 545 men who have sex with men (MSM), the rapid plasma reagin (RPR) test showed a high sensitivity of 92% for diagnosing syphilis, indicating it is effective for identifying infections in this population.

Combining serological testing with an experimental transcription-mediated amplification (TMA) assay on mucosal swabs may enhance syphilis screening sensitivity, particularly in high-risk groups, as the TMA detected additional cases that RPR alone did not identify.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treponema pallidum Nucleic Acid Amplification Testing To Augment Syphilis Screening among Men Who Have Sex with Men. Golden, M., O'Donnell, M., Lukehart, S., et al.[2020]

The new transcription-mediated amplification (TMA) assay for detecting Treponema pallidum rRNA shows high analytical sensitivity, detecting as few as 1.4 organisms/ml, and 100% positivity at 10 copies/ml, indicating it is a reliable method for identifying syphilis.

In clinical testing, the TMA assay demonstrated a 19.6% positivity rate in serum specimens from patients with known syphilis diagnoses, suggesting it could be a valuable adjunct to traditional serological tests for more accurate syphilis screening and diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analytical Performance Characteristics of a New Transcription-Mediated Amplification Assay for Treponema pallidum. Getman, D., Lin, M., Barakat, N., et al.[2022]

The Treponema pallidum PCR test demonstrated high sensitivity (94.7% for primary syphilis) and specificity (98.6% for both primary and secondary syphilis), making it a reliable method for diagnosing early syphilis in patients attending genitourinary medicine clinics in the UK.

The PCR test can detect syphilis infections earlier than serological tests, as evidenced by two HIV positive patients who tested positive by PCR before showing serological signs of infection, highlighting its potential for timely diagnosis and treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of PCR in the diagnosis of early syphilis in the United Kingdom. Palmer, HM., Higgins, SP., Herring, AJ., et al.[2019]

The Aptima® assays demonstrated high sensitivity (98.90%) and perfect specificity (100%) for detecting Chlamydia trachomatis and Neisseria gonorrhoeae, making them highly effective for STD diagnosis.

The CoBAS® assays showed 100% sensitivity but slightly lower specificity (96.67%), and they failed to detect Neisseria gonorrhoeae from anal/rectal specimens, highlighting the importance of using validated specimen types for accurate results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison between Aptima® assays (Hologic) and the CoBAS® 6800 system (Roche) for the diagnosis of sexually transmitted infections caused by Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma genitalium. Barrientos-Durán, A., de Salazar, A., Fuentes-López, A., et al.[2021]

The Aptima HIV-1 RNA qualitative assay successfully detected 100% of HIV-1 RNA in pooled samples, demonstrating its high sensitivity with detection limits of 1,070 and 2,130 copies/ml for 16- and 32-member pools, respectively.

This assay exceeds FDA requirements and is effective for screening acute-phase HIV infections, making it a valuable tool for early detection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Performance of the Aptima HIV-1 RNA qualitative assay with 16- and 32-member specimen pools. Ethridge, SF., Hart, C., Hanson, DL., et al.[2021]

The investigational transcription-mediated amplification test for Treponema pallidum (TP-TMA) identified an additional 14 syphilis infections (7% of cases) among 3283 participants in a national PrEP program, highlighting its effectiveness in enhancing syphilis detection.

The TP-TMA assay provided positive results in 41% of diagnosed syphilis cases, including instances where routine diagnostics did not detect the infection, suggesting it could significantly improve syphilis case finding and help reduce transmission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Timely diagnosis of incubating syphilis infections using Treponema pallidum Transcription Mediated Amplification assay. Zondag, HCA., van Dam, AP., Bosch, J., et al.[2023]

The most reliable method for diagnosing syphilis is the direct demonstration of Treponema pallidum in early specimens, while various serological tests like VDRL and FTA-ABS are used to detect antibodies in the blood.

The presence of 19S IgM antibodies indicates active syphilis, and their disappearance suggests successful treatment, highlighting the importance of specific tests like IgM-SPHA for monitoring disease activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnosis of syphilis. Luger, A.[2018]

The Aptima HIV-1 Quant Dx assay demonstrated high analytical sensitivity with a limit of detection of 4.9 IU/mL, making it effective for accurately measuring HIV-1 viral loads.

With a specificity of 99.83%, the Aptima assay showed comparable performance to the Roche COBAS test, detecting 90.2% of HIV-positive samples, indicating its reliability for diagnosing and monitoring HIV infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analytical characteristics and comparative evaluation of Aptima HIV-1 Quant Dx assay with Ampliprep/COBAS TaqMan HIV-1 test v2.0. Hatzakis, A., Papachristou, H., Nair, SJ., et al.[2022]

The Gen-Probe Aptima HIV-1 screening assay demonstrates 100% sensitivity and high specificity (99.4% for dried blood spots and 99.5% for whole blood), making it a highly reliable method for early HIV diagnosis in infants.

With the capability to process 1,900 samples in just 24 hours, the Aptima assay is well-suited for high-volume testing in centralized laboratories, improving access to timely diagnosis for the estimated 300,000 HIV-exposed infants in South Africa each year.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultra-high-throughput, automated nucleic acid detection of human immunodeficiency virus (HIV) for infant infection diagnosis using the Gen-Probe Aptima HIV-1 screening assay. Stevens, WS., Noble, L., Berrie, L., et al.[2021]

The Aptima HIV-1 Quant Dx Assay can detect HIV-RNA in patients with suppressed viral loads by amplifying the LTR region, revealing that some detected RNA elements (LTR-e) are incomplete and unable to cause productive infections.

LTR-e were found to be associated with cell debris rather than exosomes and did not trigger infections or cytopathic effects in laboratory tests, highlighting the importance of correctly interpreting these results to avoid unnecessary changes in patient treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Virological characterization of HIV-1 RNA elements detected exclusively through the LTR region by the dual-target Aptima HIV-1 Quant Dx assay in a subset of positive patients. Sberna, G., Nardacci, R., Berno, G., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06082453?term=molecular%20tests%20syphilis&rank=1

NCT06082453 | Modernizing Perinatal Syphilis Testing The purpose of this study is to determine the testing performance of real-time quantitative polymerase chain reaction and transcription mediated ...

2. withpower.com withpower.com/trial/phase-syphilis-4-2023-bf24b

Diagnostic Tests for Syphilis in Pregnancy The Aptima TMA assay is unique because it detects the genetic material (rRNA) of the syphilis-causing bacteria, Treponema pallidum, with high sensitivity ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33980645/

Analytical Performance Characteristics of a New ... This study evaluated the performance characteristics of a new research-use-only transcription-mediated amplification (TMA) assay for the ...

4. academic.oup.com academic.oup.com/cid/article/77/12/1717/7236758

Timely Diagnosis of Incubating Syphilis Infections Using ... The TP-TMA assay is a useful diagnostic tool to increase syphilis case finding and thus limit the transmission of syphilis.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40539791/

Advanced specificity and sensitivity studies relative to a ... A research-use-only real-time transcription-mediated amplification assay for Treponema pallidum (RUO T. pallidum TMA) yields instances of T. pallidum nucleic ...

6. hologic.com hologic.com/sites/default/files/2019-01/AW-17946_001_01.pdf

Aptima Mycoplasma genitalium assay package insert The Aptima Mycoplasma genitalium assay involves three main steps, which all take place in a single tube on the Panther system: target capture, TMA, and HPA. The ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10724458/

Timely Diagnosis of Incubating Syphilis Infections Using ... The TP-TMA assay is a useful diagnostic tool to increase syphilis case finding and thus limit the transmission of syphilis.