Clinical trial NCT02961751: Clinical Validation of a Molecular Test for Ciprofloxacin-Susceptibility in Neisseria Gonorrhoeae
Official title: Clinical Validation of a Molecular Test for Ciprofloxacin-Susceptibility in Neisseria Gonorrhoeae
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Gonococcal Infection
Keywords: Ciprofloxacin-susceptibility
Efficacy
Gyrase A Assay
Neisseria gonorrhoeae
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2016-11-11
Enrollment: 211
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The Percentage of Subjects Infected With Gyrase A (gyrA) Serine 91 Genotype of Neisseria Gonorrhoeae (N. Gonorrhoeae) With Microbiological Cure
timeFrame: Day 5 through Day 10
Secondary outcomes:
measure: The Percentage of Microbiologically Cured Subjects Who Had Urogenital Tract Infection Caused by gyrA Serine 91 Genotype N. Gonorrhoeae
timeFrame: Day 5 through Day 10
measure: The Percentage of Microbiologically Cured Subjects Who Had Rectal Infection Caused by gyrA Serine 91 Genotype N. Gonorrhoeae
timeFrame: Day 5 through Day 10
measure: The Percentage of Microbiologically Cured Subjects Who Had Throat Infection Caused by gyrA Serine 91 Genotype N. Gonorrhoeae
timeFrame: Day 5 through Day 10
measure: The Number of Subjects With Urethral Infection of gyrA Serine 91 Genotype N. Gonorrhoeae Who Have Ciprofloxacin-susceptible N. Gonorrhoeae
timeFrame: Day 1
measure: The Number of Subjects With Cervical Infection of gyrA Serine 91 Genotype N. Gonorrhoeae Who Have Ciprofloxacin-susceptible N. Gonorrhoeae
timeFrame: Day 1
measure: The Number of Subjects With Rectal Infection of gyrA Serine 91 Genotype N. Gonorrhoeae Who Have Ciprofloxacin-susceptible N. Gonorrhoeae
timeFrame: Day 1
measure: The Number of Subjects With Pharyngeal Infection of gyrA Serine 91 Genotype N. Gonorrhoeae Who Have Ciprofloxacin-susceptible N. Gonorrhoeae
timeFrame: Day 1
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: AIDS Healthcare Foundation Wellness Center - Hollywood
state: California
city: Los Angeles
country: United States
facility: Los Angeles Lesbian Gay Bisexual/Transgender Center
state: California
city: San Diego
country: United States
facility: University of California, San Diego - Antiviral Research Center
state: California
city: San Diego
country: United States
facility: University of California, San Diego Health - Owen Clinic
state: California
city: San Francisco
country: United States
facility: San Francisco Department of Public Health - San Francisco City Clinic
state: California
city: Washington
country: United States
facility: Whitman-Walker Health
state: District of Columbia
city: New Orleans
country: United States
facility: Louisiana State University Health Sciences Center
state: Louisiana
city: Jackson
country: United States
facility: University of Mississippi - Infectious Diseases
state: Mississippi
city: Philadelphia
country: United States
facility: Philadelphia Department of Public Health - Health Center 1
state: Pennsylvania
Study officials:
References:
citation: 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.