Clinical Validation of a Molecular Test for Ciprofloxacin-Susceptibility in Neisseria Gonorrhoeae

This study is a multi-center, single-arm, open-label clinical study to assess the efficacy of one dose of ciprofloxacin given orally in subjects infected with untreated gyrase A (gyrA) serine 91 genotype Neisseria gonorrhoeae (N. gonorrhoeae) as determined by a real-time Polymerase Chain Reaction (PCR) assay. The study will enroll approximately 381 subjects to obtain an eligibility target of 257 subjects, per protocol, age 18 and older regardless of gender identification who are seeking care in Sexually Transmitted Disease (STD) clinics of up to eight of the participating sites in the United States. Subjects who have untreated gyrA serine 91 genotype N. gonorrhoeae of the rectum, or male or female urogenital tract identified by a positive culture or Nucleic Acid Amplification Test (NAAT) conducted at a prior visit will be offered enrollment in the study. They will receive one dose of directly observed ciprofloxacin 500 milligrams. Subjects not consenting to participate in the study will receive treatment per local standard of care. The duration of the study for each subject will be approximately 11 through 14 days. The primary objective of this study is to determine the efficacy of ciprofloxacin for treatment of uncomplicated N. gonorrhoeae infections with gyrA serine 91 genotype.

Study Overview

• Status: Completed
• Conditions: Gonococcal Infection
• Intervention / Treatment: Drug: Ciprofloxacin

Detailed Description

This study is a multi-center, single-arm, open-label clinical study to assess the efficacy of one dose of ciprofloxacin given orally in subjects infected with untreated gyrase A (gyrA) serine 91 genotype Neisseria gonorrhoeae (N. gonorrhoeae) as determined by a real-time Polymerase Chain Reaction (PCR) assay. The study will enroll approximately 381 subjects to obtain an eligibility target of 257 subjects, per protocol, age 18 and older regardless of gender identification who are seeking care in Sexually Transmitted Disease (STD) clinics of up to eight of the participating sites in the United States. Subjects who have untreated gyrA serine 91 genotype N. gonorrhoeae of the rectum, or male or female urogenital tract identified by a positive culture or Nucleic Acid Amplification Test (NAAT) conducted at a prior visit will be offered enrollment in the study. They will receive one dose of directly observed ciprofloxacin 500 milligrams. Subjects not consenting to participate in the study will receive treatment per local standard of care. The duration of the study for each subject will be approximately 11 through 14 days. The primary objective of this study is to determine the efficacy of ciprofloxacin for treatment of uncomplicated N. gonorrhoeae infections with gyrA serine 91 genotype. The secondary objectives of the study are to 1) investigate the efficacy of ciprofloxacin for treatment of uncomplicated serine 91 gyrA N. gonorrhoeae infection by anatomic site and 2) to determine the sensitivity of the gyrA assay for detection of ciprofloxacin-susceptible N. gonorrhoeae infections.

• Study Type: Interventional
• Enrollment (Actual): 211
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027
      • AIDS Healthcare Foundation Wellness Center - Hollywood
    • Los Angeles, California, United States, 90028-6213
      • Los Angeles Lesbian Gay Bisexual/Transgender Center
    • San Diego, California, United States, 92103-8208
      • University of California, San Diego - Antiviral Research Center
    • San Diego, California, United States, 92103
      • University of California, San Diego Health - Owen Clinic
    • San Francisco, California, United States, 94103-4030
      • San Francisco Department of Public Health - San Francisco City Clinic
  • District of Columbia
    • Washington, District of Columbia, United States, 20005
      • Whitman-Walker Health
  • Louisiana
    • New Orleans, Louisiana, United States, 70119
      • Louisiana State University Health Sciences Center
  • Mississippi
    • Jackson, Mississippi, United States, 39202
      • University of Mississippi - Infectious Diseases
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19146
      • Philadelphia Department of Public Health - Health Center 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Willing and able to give voluntary written informed consent before any study related procedure is performed.
2. 18 years or older, on the day of enrollment.

3. Untreated gyrA serine 91 genotype N. gonorrhoeae of the rectum, or male or female urogenital tract, as determined by the gyrA test assay on a specimen collected within 30 days of enrollment.

   *Subjects must have gyrA serine 91 genotype detected for N. gonorrhoeae from at least one non-pharyngeal site.

4. Willing to abstain from sexual intercourse or use condoms during any sexual contact until the Test of Cure Visit (Visit 2, Day 5-10) is complete.

5. Women of childbearing potential must have no vaginal intercourse 14 days before enrollment or use an effective birth control method for 30 days before enrollment and agree to continue through visit 2.

   *A woman is considered of childbearing potential unless post-menopausal (greater than 2 years) or surgically sterilized (tubal ligation greater than 1 year, bilateral oophorectomy, or hysterectomy).

   **Acceptable birth control methods for the purposes of this study may include abstinence from intercourse with a male partner, monogamous relationship with vasectomized partner, male condoms with the use of applied spermicide, intrauterine devices, and licensed hormonal methods. A highly effective method of contraception is defined as one that results in a low failure rate (i.e., less than 1 percent per year) when used consistently and correctly.

6. Able to swallow pills.
7. Willing to comply with protocol requirements, including availability for follow-up for the duration of the study.
8. Agree to avoid systemic or intravaginal antibiotics with activity against N. gonorrhoeae from enrollment through Visit 2 (Day 5-10). Topical and intravaginal antifungals are permitted.
9. Agree to avoid magnesium/aluminum antacids, sucralfate, didanosine, or highly buffered drugs, up to 2 hours after receipt of study drug.

Exclusion Criteria:

1. Known renal insufficiency from clinical history.

2. Use of systemic or intravaginal antibiotics with potential activity against N. gonorrhoeae within 30 days prior to study drug administration.

   *Topical and intravaginal antifungals are permitted.

3. Use of systemic corticosteroid drugs or other immunosuppressive therapy within 30 days prior to enrollment.
4. Receipt or planned receipt of an investigational product in a clinical trial within 30 days prior to or 7 days after treatment administration.
5. Pregnant or breastfeeding.
6. Clinical diagnosis of pelvic inflammatory disease or genital ulcer.
7. Confirmed or suspected complicated or systemic gonococcal infection, such as abdominal pain, testicular pain, epididymitis, orchitis, arthritis, or endocarditis.
8. Receipt of magnesium/aluminum antacids, sucralfate, didanosine, or highly buffered drugs, within 6 hours before receipt of study drug.
9. Mutant N. gonorrhoeae gyrA serine 91 genotype from any anatomic site, as determined by the gyrA test assay on a specimen collected within 30 days of enrollment.
10. Known allergy or history of adverse reaction to ciprofloxacin.
11. Known allergy to quinolones.
12. Previous enrollment in this study.
13. Medical condition or other factor that in the judgment of the investigator might affect ability to comply with procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Ciprofloxacin; One dose of directly-observed ciprofloxacin 500 mg administered orally. N=381	Drug: Ciprofloxacin; Directly observed treatment with a single dose of ciprofloxacin 500 mg orally with or without food.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percentage of Subjects Infected With Gyrase A (gyrA) Serine 91 Genotype of Neisseria Gonorrhoeae (N. Gonorrhoeae) With Microbiological Cure	Subjects infected with gyrase A (gyrA) serine 91 genotype of Neisseria gonorrhoeae (N. gonorrhoeae) were evaluated for microbiological cure at 5-10 days after treatment. Cure was defined as N. gonorrhoeae not detectable by culture from all anatomical sites that had detectable N. gonorrhoeae at baseline.	Day 5 through Day 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percentage of Microbiologically Cured Subjects Who Had Urogenital Tract Infection Caused by gyrA Serine 91 Genotype N. Gonorrhoeae	Subjects infected with gyrase A (gyrA) serine 91 genotype of Neisseria gonorrhoeae (N. gonorrhoeae) at the urogenital tract were evaluated for microbiological cure at 5-10 days after treatment. Cure was defined as N. gonorrhoeae not detectable by culture from all anatomical sites that had detectable N. gonorrhoeae at baseline	Day 5 through Day 10
The Percentage of Microbiologically Cured Subjects Who Had Rectal Infection Caused by gyrA Serine 91 Genotype N. Gonorrhoeae	Subjects infected with gyrase A (gyrA) serine 91 genotype of Neisseria gonorrhoeae (N. gonorrhoeae) at the rectum were evaluated for microbiological cure at 5-10 days after treatment. Cure was defined as N. gonorrhoeae not detectable by culture from all anatomical sites that had detectable N. gonorrhoeae at baseline	Day 5 through Day 10
The Percentage of Microbiologically Cured Subjects Who Had Throat Infection Caused by gyrA Serine 91 Genotype N. Gonorrhoeae	Subjects infected with gyrase A (gyrA) serine 91 genotype of Neisseria gonorrhoeae (N. gonorrhoeae) at the throat were evaluated for microbiological cure at 5-10 days after treatment. Cure was defined as N. gonorrhoeae not detectable by culture from all anatomical sites that had detectable N. gonorrhoeae at baseline	Day 5 through Day 10
The Number of Subjects With Urethral Infection of gyrA Serine 91 Genotype N. Gonorrhoeae Who Have Ciprofloxacin-susceptible N. Gonorrhoeae	Ciprofloxacin susceptibility was determined via culture-based antimicrobial susceptibility testing of the gonococcal isolate from each urethral sample with a positive N. gonorrhoeae culture at Visit 1. An infection was deemed susceptible to ciprofloxacin if the reported minimum inhibitory concentration for the isolate was < 1 mcg/ml. Detection of wild type gyrA was determined by the real-time PCR analysis of the gyrA gene from the swab taken at Visit 1.	Day 1
The Number of Subjects With Cervical Infection of gyrA Serine 91 Genotype N. Gonorrhoeae Who Have Ciprofloxacin-susceptible N. Gonorrhoeae	Ciprofloxacin susceptibility was determined via culture-based antimicrobial susceptibility testing of the gonococcal isolate from each cervical sample with a positive N. gonorrhoeae culture at Visit 1. An infection was deemed susceptible to ciprofloxacin if the reported minimum inhibitory concentration for the isolate was < 1 mcg/ml. Detection of wild type gyrA was determined by the real-time PCR analysis of the gyrA gene from the swab taken at Visit 1.	Day 1
The Number of Subjects With Rectal Infection of gyrA Serine 91 Genotype N. Gonorrhoeae Who Have Ciprofloxacin-susceptible N. Gonorrhoeae	Ciprofloxacin susceptibility was determined via culture-based antimicrobial susceptibility testing of the gonococcal isolate from each rectal sample with a positive N. gonorrhoeae culture at Visit 1. An infection was deemed susceptible to ciprofloxacin if the reported minimum inhibitory concentration for the isolate was < 1 mcg/ml. Detection of wild type gyrA was determined by the real-time PCR analysis of the gyrA gene from the swab taken at Visit 1.	Day 1
The Number of Subjects With Pharyngeal Infection of gyrA Serine 91 Genotype N. Gonorrhoeae Who Have Ciprofloxacin-susceptible N. Gonorrhoeae	Ciprofloxacin susceptibility was determined via culture-based antimicrobial susceptibility testing of the gonococcal isolate from each pharyngeal sample with a positive N. gonorrhoeae culture at Visit 1. An infection was deemed susceptible to ciprofloxacin if the reported minimum inhibitory concentration for the isolate was < 1 mcg/ml. Detection of wild type gyrA was determined by the real-time PCR analysis of the gyrA gene from the swab taken at Visit 1.	Day 1

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Publications and helpful links

General Publications

• Klausner JD, Bristow CC, Soge OO, Shahkolahi A, Waymer T, Bolan RK, Philip SS, Asbel LE, Taylor SN, Mena LA, Goldstein DA, Powell JA, Wierzbicki MR, Morris SR. Resistance-Guided Treatment of Gonorrhea: A Prospective Clinical Study. Clin Infect Dis. 2021 Jul 15;73(2):298-303. doi: 10.1093/cid/ciaa596. Erratum In: Clin Infect Dis. 2021 Mar 1;72(5):911.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 19, 2016
• Primary Completion (ACTUAL): January 4, 2019
• Study Completion (ACTUAL): January 4, 2019

Study Registration Dates

• First Submitted: November 9, 2016
• First Submitted That Met QC Criteria: November 9, 2016
• First Posted (ESTIMATE): November 11, 2016

Study Record Updates

• Last Update Posted (ACTUAL): August 25, 2020
• Last Update Submitted That Met QC Criteria: August 20, 2020
• Last Verified: December 4, 2019

More Information

Terms related to this study

• Keywords: Efficacy; Neisseria gonorrhoeae; Ciprofloxacin-susceptibility; Gyrase A Assay
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Communicable Diseases; Sexually Transmitted Diseases; Disease Attributes; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Neisseriaceae Infections; Sexually Transmitted Diseases, Bacterial; Disease Susceptibility; Gonorrhea; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Ciprofloxacin
• Other Study ID Numbers: 15-0090

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No