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Gent for Pharyngeal Gonorrhea (GC)

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ClinicalTrials.gov Identifier: NCT03632109
Recruitment Status : Recruiting
First Posted : August 15, 2018
Last Update Posted : October 10, 2018
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
Lindley Barbee, University of Washington

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.

Condition or disease Intervention/treatment Phase
Pharyngeal Gonococcal Infection Drug: gentamicin 360mg IM Phase 2 Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Gentamicin for Pharyngeal Gonorrhea - A Demonstration Study
Actual Study Start Date : September 17, 2018
Estimated Primary Completion Date : May 2019
Estimated Study Completion Date : July 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Gonorrhea

Arm Intervention/treatment
Experimental: Single Arm
Men who have sex with men (MSM) with pharyngeal gonorrhea will be treated with 360mg intramuscular gentamicin x 1.
Drug: gentamicin 360mg IM
360mg IM of gentamicin




Primary Outcome Measures :
  1. Cure Rate defined as the proportion of persons with pharyngeal gonorrhea treated with gentamicin 360mg IM who have a negative culture 4-7 days following treatment [ Time Frame: 4-7 days (+/- 1 day) after treatment ]
    Negative Pharyngeal Culture


Secondary Outcome Measures :
  1. Renal Safety as measured by a change in serum creatinine from before treatment to 4-7 days following treatment [ Time Frame: 4-7 days (+/- 1 day) after treatment ]
    A >=40% increase in serum Creatinine

  2. Tolerability of gentamicin 360mg IM x 1: Adverse events [ Time Frame: 4-7 days (+/- 1 day) after treatment ]
    Adverse events as described by subjects' responses to standardized side effect questionnaire at the TOC visit

  3. Peak Gentamicin levels [ Time Frame: at 30, 45, or 60 minutes post dose ]
    serum gentamicin concentration

  4. Gentamicin minimal inhibitory concentration (MIC) [ Time Frame: baseline/enrollment visit ]
    laboratory defined MIC of infecting strain of N. gonorrhoeae at enrollment visit determined by agar dilution


Other Outcome Measures:
  1. Exploratory study: look for evidence of induced resistance [ Time Frame: 4-7 days (+/- 1 day) after treatment ]
    Among treatment failures, compare pre-treatment and post-treatment minimal inhibitory concentrations (MIC)



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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03632109


Contacts
Contact: Lindley A Barbee, MD, MPH 206-744-2595 lbarbee@uw.edu

Locations
United States, Washington
Public Health -- Seattle & King County STD Clinic Recruiting
Seattle, Washington, United States, 98104
Contact: Angela LeClaire    206-744-4089      
Sponsors and Collaborators
University of Washington
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Principal Investigator: Lindley A Barbee, MD, MPH University of Washington

Responsible Party: Lindley Barbee, Assistant Professor, School of Medicine: Department of Medicine: Allergy and Infectious Diseases, University of Washington
ClinicalTrials.gov Identifier: NCT03632109     History of Changes
Other Study ID Numbers: STUDY00003878
K23AI113185 ( U.S. NIH Grant/Contract )
First Posted: August 15, 2018    Key Record Dates
Last Update Posted: October 10, 2018
Last Verified: October 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Lindley Barbee, University of Washington:
gonorrhea
pharynx
treatment
gentamicin

Additional relevant MeSH terms:
Gonorrhea
Neisseriaceae Infections
Gram-Negative Bacterial Infections
Bacterial Infections
Sexually Transmitted Diseases, Bacterial
Sexually Transmitted Diseases
Infection
Genital Diseases, Male
Genital Diseases, Female
Gentamicins
Anti-Bacterial Agents
Anti-Infective Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action