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Gent for Pharyngeal Gonorrhea (GC)

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ClinicalTrials.gov Identifier: NCT03632109
Recruitment Status : Terminated (Efficacy)
First Posted : August 15, 2018
Results First Posted : August 10, 2020
Last Update Posted : August 10, 2020
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
Lindley Barbee, University of Washington

Tracking Information
First Submitted Date  ICMJE July 3, 2018
First Posted Date  ICMJE August 15, 2018
Results First Submitted Date  ICMJE July 6, 2020
Results First Posted Date  ICMJE August 10, 2020
Last Update Posted Date August 10, 2020
Actual Study Start Date  ICMJE September 17, 2018
Actual Primary Completion Date March 12, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 24, 2020)
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 [ Time Frame: 4-7 days (+/- 1 day) after treatment ]
Negative Pharyngeal Culture
Original Primary Outcome Measures  ICMJE
 (submitted: August 14, 2018)
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
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 24, 2020)
  • Renal Safety [ Time Frame: 4-7 days (+/- 1 day) after treatment ]
    Measured by a percent change in serum creatinine from baseline to test of cure (4-7 days following treatment)
  • Tolerability of the Injection Gentamicin 360mg IM x 1 [ Time Frame: 4-7 days (+/- 1 day) after treatment ]
    Participant reported pain scale, with 1 being little to no pain, and 10 being the worst pain ever.
  • Peak Gentamicin Levels [ Time Frame: at 30, 45, or 60 minutes post dose ]
    serum gentamicin concentration
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: August 14, 2018)
  • 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
  • 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
  • Peak Gentamicin levels [ Time Frame: at 30, 45, or 60 minutes post dose ]
    serum gentamicin concentration
  • 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
Current Other Pre-specified Outcome Measures
 (submitted: July 6, 2020)
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)
Original Other Pre-specified Outcome Measures
 (submitted: August 14, 2018)
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)
 
Descriptive Information
Brief Title  ICMJE Gent for Pharyngeal Gonorrhea (GC)
Official Title  ICMJE Gentamicin for Pharyngeal Gonorrhea - A Demonstration Study
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pharyngeal Gonococcal Infection
Intervention  ICMJE Drug: gentamicin 360mg IM
360mg IM of gentamicin
Study Arms  ICMJE Experimental: Single Arm
Men who have sex with men (MSM) with pharyngeal gonorrhea will be treated with 360mg intramuscular gentamicin x 1.
Intervention: Drug: gentamicin 360mg IM
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: April 5, 2019)
13
Original Estimated Enrollment  ICMJE
 (submitted: August 14, 2018)
60
Actual Study Completion Date  ICMJE March 12, 2019
Actual Primary Completion Date March 12, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03632109
Other Study ID Numbers  ICMJE STUDY00003878
K23AI113185 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Lindley Barbee, University of Washington
Study Sponsor  ICMJE University of Washington
Collaborators  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Investigators  ICMJE
Principal Investigator: Lindley A Barbee, MD, MPH University of Washington
PRS Account University of Washington
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP