Identification of Herpes Simplex Virus (HSV) Shedding in the Female Genital Tract of Pregnant and Nonpregnant Women by GeneXpert PCR, Routine PCR, and Culture

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by University of Alabama at Birmingham
Sponsor:
Information provided by (Responsible Party):
David Kimberlin, MD, University of Alabama at Birmingham
ClinicalTrials.gov Identifier:
NCT01878383
First received: June 12, 2013
Last updated: August 29, 2014
Last verified: August 2014
  Purpose

PCR detection of HSV DNA shedding in the female genital tract using the GeneXpert system (Cepheid, Sunnyvale CA) will be compared with traditional (routine) PCR (pregnant and nonpregnant women) and with HSV culture (nonpregnant women). The GeneXpert system performs all sample-processing steps and real-time PCR in a single integrated cartridge. The standard cartridge is an inexpensive disposable plastic cartridge with filtration and ultrasonic lysis capabilities. It consists chiefly of several combined molded plastic components: a cartridge body containing eleven fluid reservoirs or chambers along with an attached PCR tube, a specialized valve body with an ultrasonic interface containing a sub-micron filter and glass lysis beads, and a rotary valve with an axial syringe barrel. The operation of the cartridge is simple. The rotary valve contains an inlet and an outlet port. Fluid such as a sample buffer can be drawn up into a syringe drive through the inlet port of the rotary valve and then dispensed into any other chamber within the cartridge by rotating the valve and expelling the fluid through the outlet port. The fluid can either be passed through a filter contained within the valve assembly or it can be passed directly into the next chamber without filtration, depending on the path that is chosen. The cartridge fluidics and subsequent real-time PCR all are performed within the GeneXpert instrument. The GeneXpert contains multiple modules (ICORE units) that can be independently programmed to drive the syringe/rotary valve, and to perform four-color real-time PCR. Each cartridge fits inside one module, and all processing, PCR, and analysis steps are performed automatically. Each ICORE module can be run and analyzed independently, so batching of samples is unnecessary.


Condition Intervention
Herpes Simplex Virus
Device: Genexpert assay

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Device Trial: Identification of Herpes Simplex Virus (HSV) Shedding in the Female Genital Tract of Pregnant and Nonpregnant Women by GeneXpert PCR, Routine PCR, and Culture

Resource links provided by NLM:


Further study details as provided by University of Alabama at Birmingham:

Primary Outcome Measures:
  • Sensitivity of detection of HSV DNA by GeneXpert PCR from specimens obtained from the genital tract of pregnant women in active labor or of non-pregnant women in STI clinics, as compared with routine PCR detection of viral DNA (pregnant and nonpregnant [ Time Frame: on day of enrollment ] [ Designated as safety issue: No ]
    assessing the vaginal specimen collected via a swab at the time of reported active labor with standard PCR compared to the assay of new device called a GeneXpert


Secondary Outcome Measures:
  • HSV disease among neonates delivered to women without active genital HSV lesions Specificity, positive predictive value, and negative predictive value of detection of HSV DNA by GeneXpert PCR from specimens obtained from the genital tract of pregnant [ Time Frame: day of enrollment ] [ Designated as safety issue: No ]

Estimated Enrollment: 12500
Study Start Date: January 2014
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Non-pregnant women/active HSV lesions
Women presenting to local health department
Device: Genexpert assay
Pregnant women/no active HSV lesions
Women presenting in active labor
Device: Genexpert assay

Detailed Description:

The GeneXpert HSV PCR test will be validated against HSV viral cultures and routine quantitative PCR. Validation will occur in two populations: 1) nonpregnant women in STI clinics with clinically-apparent HSV lesions (Group 1, n=300), and 2) pregnant women in active labor with no visible evidence of HSV infection (Group 2, n=12,500). All testing of samples on the GeneXpert platform, routine quantitative PCR, and viral culture will be done at the UAB Central Laboratory. Women in each group will have specimens obtained from genital lesions (Group 1) or vaginal swabs (Group 2). Specimens from all women in Group 1 will be evaluated by HSV culture, routine HSV PCR, and GeneXpert HSV PCR. Approximately half of the women in Group 2 will be tested by routine HSV PCR and GeneXpert HSV PCR; specimens from the rest of the women in Group 2 will be stored for possible testing in the future by routine HSV PCR and GeneXpert HSV PCR. In this manner, we will maximize the data from which to compare GeneXpert PCR results with routine PCR, while maintaining flexibility to ensure an adequate number of specimens are positive for HSV DNA by routine PCR.

Swabs from pregnant women in labor will be placed in viral transport media, frozen at -20°C, and batch-shipped to the UAB Central Laboratory for analysis on the GeneXpert instrument and by routine HSV quantitative PCR. Swabs from nonpregnant women in STI clinics will be placed in viral transport media, refrigerated at 4°C, and shipped to the UAB Central Laboratory for real time analysis on the GeneXpert instrument and by HSV culture and routine quantitative HSV PCR. Specimens from the first 300 women enrolled in Group 2 will be run as individual routine PCRs and in batches of 5 samples per PCR run. In this manner, we will validate that the level of detection from batching of samples for routine PCR is acceptable. Once this validation occurs, specimens from the approximately half of remaining Group 2 women will be batched for real-time routine PCR analysis. If a batch run of 5 specimens is negative, no further testing will be performed. If a batch run of 5 specimens is positive, all of the specimens will be separated out for re-running as individual PCRs. All specimens evaluated by routine PCR will also be evaluated by GeneXpert PCR; in this manner, we will have individual routine PCR results results for comparison against GeneXpert PCR results.

A blood specimen will be obtained from each nonpregnant (Group 1) and pregnant (Group 2) woman at the time of enrollment, and if she is determined to be shedding HSV by routine PCR, GeneXpert PCR, or culture then type-specific serologic testing will be performed. Correlation of viral typing from the virologic sampling with HSV-1 and HSV-2 serostatus will allow for categorization of infection (first-episode primary, first-episode nonprimary, or recurrent infection).

Those women in Group 1 who have a positive HSV culture will be contacted directly when the result is known. Women in Group 2 with a positive HSV PCR result will not be contacted because routine HSV PCR and GeneXpert PCR are not FDA-cleared tests in this population; thus, we will not know the test performance characteristics (e.g., sensitivity, specificity, etc.) until completion of the trial. All pregnant women in Group 2 will receive written materials at the time of enrollment educating them on signs and symptoms of neonatal HSV disease. All postpartum women will be contacted by telephone 60-90 days post-delivery and an inquiry will be made to determine if their babies developed neonatal HSV disease.

Data on the incidence of neonatal HSV disease among babies delivered to women in Group 2 will be compared with the incidence data from Brown et al.1 In their study of almost 60,000 women conducted over a 20 year period, this group of researchers has reported an incidence rate for neonatal HSV disease of 1 in 3,200 live births.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Pregnant and non-pregnant women

Criteria

Inclusion Criteria:•Signed Informed Consent from woman

•≥ 19 years of age

  • Female gender
  • In active labor with a viable fetus, OR non-pregnant and being evaluated in STI clinics for herpetic genital lesions

Exclusion Criteria:•For women in active labor, active herpetic lesions in the genital region

  • Receipt of acyclovir, valacyclovir, or famciclovir within the previous 14 days
  • Known HIV infection
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01878383

Contacts
Contact: Ilet Dale, RN 205-934-2424 idale@peds.uab.edu
Contact: Penelope M Jester, RN 205-934-2424 pjester@peds.uab.edu

Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35233
Contact: David Kimberlin, M.D.    205-934-5316    Dkimberlin@peds.uab.edu   
Principal Investigator: David Kimberlin, M.D.         
United States, Arkansas
University of Arkansas for Medical Sciences Recruiting
Little Rock, Arkansas, United States, 72202
Contact: Jose Romero, MD    501-364-1416    RomeroJose@uams.edu   
Principal Investigator: Jose Romero, MD         
United States, Colorado
University of Colorado at Denver Health Sciences Center Not yet recruiting
Aurora, Colorado, United States, 80045
Contact: Mark J Abzug, M.D.    720-777-6389    abzug.mark@tchden.org   
Principal Investigator: Mark J Abzug, M.D.         
United States, District of Columbia
Children's National Medical Center Recruiting
Washington, District of Columbia, United States, 20010
Contact: Roberta L DeBiasi, MD    202-476-5051    rdebiasi@cnmc.org   
Principal Investigator: Roberta L DeBiasi, MD         
United States, Georgia
Emory Children's Center Recruiting
Atlanta, Georgia, United States, 30322
Contact: Andrea (Andi) Shane, M.D., M.P.H.    404-727-4044    vaccinestudy@oz.ped.emory.edu   
Principal Investigator: Andrea (Andi) Shane, M.D., M.P.H.         
United States, Louisiana
Louisiana State University Health Science Center-Shreveport Recruiting
Shreveport, Louisiana, United States, 71103
Contact: John Vanchiere, MD, PhD    318-675-7877    jvanch@Isuhsc.edu   
Principal Investigator: John Vanchiere, MD, PhD         
United States, Missouri
Washington University in St Louis School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Contact: Gregory Storch, M.D.    314-454-6079    storch_G@kids.wustl.edu   
Principal Investigator: Gregory Storch, M.D.         
United States, New Hampshire
Dartmouth Medical School Recruiting
Lebanon, New Hampshire, United States, 03756
Contact: Peter F Wright, M.D.    603-653-6190    peter.f.wright@dartmouth.edu   
Principal Investigator: Peter F Wright, M.D.         
United States, New York
Steven & Alexandra Cohen Children's Medical Center of New York (CCMC) Recruiting
Manhasset, New York, United States, 11030
Contact: Sunil Sood, MD    516-562-3957    sood@lij.edu   
Principal Investigator: Sunil Sood, MD         
University of Rochester Medical Center Recruiting
Rochester, New York, United States, 14642
Contact: Mary Caserta, M.D.    585-275-5944    mary_caserta@urmc.rochester.edu   
Principal Investigator: Mary Caserta, M.D.         
United States, North Carolina
Carolinas Medical Center - Charlotte Recruiting
Charlotte, North Carolina, United States, 28203
Contact: Amina Ahmed, M.D.B.S    704-381-6870    Amina.ahmed@carolinashealthcare.org   
Principal Investigator: Amina Ahmed, M.D.B.S.         
United States, Ohio
MetroHealth Medical Center Recruiting
Cleveland, Ohio, United States, 44109
Contact: Nazha F Abughali, M.D.    216-778-3402    nabughali@metrohealth.org   
Principal Investigator: Nazha F Abughali, M.D.         
Nationwide Children Hospital Not yet recruiting
Columbus, Ohio, United States, 43205-2664
Contact: Pablo Sanchez, MD    614-355-5724    pablo.sanchez@nationwidechildrens.org   
Principal Investigator: Pablo Sanchez, MD         
United States, Pennsylvania
McGee Women's Hospital Not yet recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Harold Wiesenfeld, MD    412-692-6786    marian.michaels@chp.edu   
Principal Investigator: Harold Wiesenfeld, MD         
United States, Utah
University of Utah School of Medicine Recruiting
Salt Lake City, Utah, United States, 84132
Contact: Kwabena Ampofo, MD    801-581-6791    krow.ampofo@hsc.utah.edu   
Principal Investigator: Kwabena Ampofo, MD         
Sponsors and Collaborators
University of Alabama at Birmingham
Investigators
Principal Investigator: David W Kimberlin, MD University of Alabama at Birmingham
Principal Investigator: Richard Whitley, MD University of Alabama at Birmingham
  More Information

No publications provided

Responsible Party: David Kimberlin, MD, Principal Investigator, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT01878383     History of Changes
Other Study ID Numbers: DMID 11-0070
Study First Received: June 12, 2013
Last Updated: August 29, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Alabama at Birmingham:
(HSV)

Additional relevant MeSH terms:
Herpes Simplex
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Skin Diseases, Viral
Skin Diseases, Infectious
Skin Diseases

ClinicalTrials.gov processed this record on October 02, 2014