Pharyngeal Gonococcal Infection Clinical Trial
Official title:
Gentamicin for Pharyngeal Gonorrhea - A Demonstration Study
| Verified date | July 2020 |
| Source | University of Washington |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Terminated |
| Enrollment | 13 |
| Est. completion date | March 12, 2019 |
| Est. primary completion date | March 12, 2019 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 16 Years and older |
| Eligibility |
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 |
| Country | Name | City | State |
|---|---|---|---|
| United States | Public Health -- Seattle & King County STD Clinic | Seattle | Washington |
| Lead Sponsor | Collaborator |
|---|---|
| University of Washington | National Institute of Allergy and Infectious Diseases (NIAID) |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Exploratory Study: Look for Evidence of Induced Resistance | Among treatment failures, compare pre-treatment and post-treatment minimal inhibitory concentrations (MIC) | 4-7 days (+/- 1 day) after treatment | |
| Primary | 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 | Negative Pharyngeal Culture | 4-7 days (+/- 1 day) after treatment | |
| Secondary | Renal Safety | Measured by a percent change in serum creatinine from baseline to test of cure (4-7 days following treatment) | 4-7 days (+/- 1 day) after treatment | |
| Secondary | Tolerability of the Injection Gentamicin 360mg IM x 1 | Participant reported pain scale, with 1 being little to no pain, and 10 being the worst pain ever. | 4-7 days (+/- 1 day) after treatment | |
| Secondary | Peak Gentamicin Levels | serum gentamicin concentration | at 30, 45, or 60 minutes post dose | |
| Secondary | Gentamicin Minimal Inhibitory Concentration (MIC) | laboratory defined MIC of infecting strain of N. gonorrhoeae at enrollment visit determined by agar dilution | baseline/enrollment visit |