Gent for Pharyngeal Gonorrhea (GC)

NCT ID: NCT03632109

Last Updated: 2020-08-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-17
• Study Completion Date: 2019-03-12

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.

Conditions

Pharyngeal Gonococcal Infection

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single Arm

Men who have sex with men (MSM) with pharyngeal gonorrhea will be treated with 360mg intramuscular gentamicin x 1.

Group Type: EXPERIMENTAL

gentamicin 360mg IM

Intervention Type: DRUG

360mg IM of gentamicin

Interventions

gentamicin 360mg IM

360mg IM of gentamicin

Intervention Type: DRUG

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

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

University of Washington

OTHER

Sponsor Role: lead

Responsible Party

Lindley Barbee

Assistant Professor, School of Medicine: Department of Medicine: Allergy and Infectious Diseases

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lindley A Barbee, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

University of Washington

Locations

Public Health -- Seattle & King County STD Clinic

Seattle, Washington, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 31712813 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

K23AI113185

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY00003878

Identifier Type: -

Identifier Source: org_study_id