Clinical trial NCT03632109: Gent for Pharyngeal Gonorrhea (GC)
Official title: Gentamicin for Pharyngeal Gonorrhea - A Demonstration Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Pharyngeal Gonococcal Infection
Keywords: gonorrhea
pharynx
treatment
gentamicin
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2018-08-15
Enrollment: 13
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The Centers for Disease Control and Prevention has identified antimicrobial-resistant (AMR) Neisseria gonorrhoeae (NG) as one of the nation's top three urgent AMR threats. Since the advent of antibiotics in the 1930s, NG has developed resistance to every first-line antibiotic. Parenteral third-generation cephalosporins are now the only class of drug with consistent efficacy against NG. New therapies are urgently needed. Although some novel antimicrobials are under development, reevaluating older drugs is another option for quickly identifying additional treatments for gonorrhea. We propose a demonstration study to test a single dose of gentamicin for the treatment of pharyngeal gonorrhea. We chose to focus on pharyngeal gonorrhea because these infections are common, play an important role in fostering gonococcal resistance, and are harder to eradicate than genital infections. Although gentamicin is 91% efficacious for genital NG, its efficacy at the pharynx may be less since streptomycin, another aminoglycoside previously used to treat gonorrhea, was not effective for pharyngeal NG. It is unknown if streptomycin's poor efficacy is indicative of limitations of aminoglycosides as a class. We plan to enroll 60 men who have sex with men in a demonstration study to be conducted at the Seattle \& King County STD Clinic to test the efficacy of 360 mg of gentamicin given intramuscularly for pharyngeal gonorrhea. Secondary objectives include determining the ideal pharmacodynamic criterion (comparing in vitro minimal inhibitory concentrations (MIC) of NG to peak gentamicin serum levels), estimating resistance induction among treatment failures, and assessing the tolerability of 360 mg of IM gentamicin.

Objectives

The proposed study aims to evaluate the efficacy of a single intramuscular (IM) dose of gentamicin in the treatment of pharyngeal gonorrhea. Secondary objectives include documenting the efficacy stratified by minimal inhibitory concentration (MIC) compared with the gentamicin peak level in order to estimate a pharmacodynamic criterion. We will also attempt to determine whether gentamicin monotherapy induces antimicrobial resistance among treatment failures. Lastly, we will evaluate the tolerability of 360 mg of IM gentamicin, stratified by subject weight (i.e. weight based dosing). The specific aims are:

1. Determine the proportion of persons whose pharyngeal gonococcal infections are cured with a single dose of 360mg gentamicin intramuscularly alone.
2. Evaluate the renal safety and tolerability of 360mg IM of gentamicin.
3. Document mean peak gentamicin levels following 360mg IM of gentamicin stratified by weight.
4. Estimate the best pharmacodynamics criterion (i.e. peak/MIC ratio) for pharyngeal gonorrhea treated with gentamicin using individual and mean peak gentamicin levels and NG isolate MIC.
5. Among treatment failures, conduct exploratory analyses comparing pre- and post-treatment MIC for evidence of induced resistance.


Eligibility criteria: Inclusion Criteria:

* Persons diagnosed with pharyngeal gonorrhea who are not yet treated

Exclusion Criteria:

* Age less than 16 years
* Receipt of antibiotics in ≤30 days
* Known allergy to any aminoglycoside
* History of renal disease (including diagnosis of solitary kidney, chronic renal insufficiency, renal cell carcinoma etc),
* Use of concurrent nephrotoxic drugs or muscle relaxants
* History of diabetes
* History of hearing loss or tinnitus
* Concurrent infection with syphilis or chlamydia
* Pregnancy and/or nursing
* Unable to return for a follow-up visit 4-7 days (+/- 1 day).
* Study team's discretion

Primary outcomes:
measure: Cure Rate Defined as the Percentage of Persons With Pharyngeal Gonorrhea Treated With Gentamicin 360mg IM Who Have a Negative Culture 4-7 Days Following Treatment
timeFrame: 4-7 days (+/- 1 day) after treatment
Secondary outcomes:
measure: Renal Safety
timeFrame: 4-7 days (+/- 1 day) after treatment
measure: Tolerability of the Injection Gentamicin 360mg IM x 1
timeFrame: 4-7 days (+/- 1 day) after treatment
measure: Peak Gentamicin Levels
timeFrame: at 30, 45, or 60 minutes post dose
measure: Gentamicin Minimal Inhibitory Concentration (MIC)
timeFrame: baseline/enrollment visit
Other outcomes:
measure: Exploratory Study: Look for Evidence of Induced Resistance
timeFrame: 4-7 days (+/- 1 day) after treatment
Locations:
city: Seattle
country: United States
facility: Public Health -- Seattle & King County STD Clinic
state: Washington
Study officials:
affiliation: University of Washington
name: Lindley A Barbee, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Barbee LA, Soge OO, Morgan J, Leclair A, Bass T, Werth BJ, Hughes JP, Golden MR. Gentamicin Alone Is Inadequate to Eradicate Neisseria Gonorrhoeae From the Pharynx. Clin Infect Dis. 2020 Nov 5;71(8):1877-1882. doi: 10.1093/cid/ciz1109.