Aztreonam for Pharyngeal Gonorrhea
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|ClinicalTrials.gov Identifier: NCT03867734|
Recruitment Status : Completed
First Posted : March 8, 2019
Last Update Posted : October 18, 2019
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 aztreonam 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 aztreonam appears to be >98.6% efficacious for anogenital NG, its efficacy at the pharynx may be less. Only 8 cases of pharyngeal gonorrhea have been documented to be treated with aztreonam, but of those, only 5 (62.5%) were cured. The dose used in those studies was 1g of aztreonam. Most antibiotics have a lower efficacy at the pharynx than anogenital sites, which is likely due to drug pharmacokinetics, i.e. difficulty in penetrating pharyngeal tissue. Thus, in the proposed study, we plan to treat 50 subjects with untreated pharyngeal gonorrhea with 2g IM Aztreonam.
The proposed study aims to evaluate the efficacy of a single 2g intramuscular (IM) dose of aztreonam in the treatment of pharyngeal gonorrhea. Secondary objectives include documenting the efficacy stratified by minimal inhibitory concentration (MIC) compared with the previously document area under the curve (AUC) in order to estimate a pharmacodynamic criterion. We will also attempt to determine whether aztreonam monotherapy induces antimicrobial resistance among treatment failures. Lastly, we will evaluate the tolerability of 2g of IM aztreonam. The specific aims are:
- Determine the proportion of persons whose pharyngeal gonococcal infections are cured with a single dose of 2g aztreonam intramuscularly.
- Determine the proportion of persons with urethral and/or rectal gonorrhea whose infections are cured with a single dose of 2g aztreonam IM.
- Evaluate the tolerability of 2g IM of aztreonam .
- Estimate the best pharmacodynamics criterion (i.e. AUC/MIC ratio) for pharyngeal gonorrhea treated with aztreonam using previously published AUC for 2g aztreonam and NG isolate MIC.
- Among treatment failures, conduct exploratory analyses comparing pre- and post-treatment MIC for evidence of induced resistance.
Study Design: Prospective cohort
Study Population & Inclusion Criteria:
Persons diagnosed with pharyngeal gonorrhea or gonococcal urethritis who are undergoing pharyngeal gonorrhea testing, who are not yet treated.
Intervention: 2g IM aztreonam x 1
Primary Outcome: Negative gonorrhea culture 4-7 days (+/- 1 day) after treatment
Sample Size: 50 persons
|Condition or disease||Intervention/treatment||Phase|
|Gonorrhea of Pharynx Gonorrhea||Drug: Aztreonam||Phase 2 Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||32 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Demonstration Study|
|Masking:||None (Open Label)|
|Official Title:||Aztreonam for Pharyngeal Gonorrhea: A Demonstration Study|
|Actual Study Start Date :||April 5, 2019|
|Actual Primary Completion Date :||September 30, 2019|
|Actual Study Completion Date :||September 30, 2019|
Experimental: 2g Aztreonam
Subjects to receive 2g Aztreonam IM for the treatment of gonorrhea
2g IM Aztreonam
- Treatment Efficacy of Pharyngeal Gonorrhea as defined as the proportion of study participants with positive pharyngeal gonorrhea culture at of enrollment whose test of cure pharyngeal culture is negative [ Time Frame: 4-7 days following treatment ]Negative Test of Cure (i.e. Pharyngeal Gonorrhea Culture) after Treatment
- Treatment Efficacy of Urethral Gonorrhea as defined as The proportion of study participants with gonococcal urethritis at enrollment whose test of cure urethral culture is negative [ Time Frame: 4-7 days following treatment ]Negative Test of Cure (I.e. Urethral gonorrhea Culture) after treatment
- Treatment Efficacy of Rectal Gonorrhea as defined as The proportion of study participants with positive rectal culture at enrollment whose test of cure rectal culture is negative [ Time Frame: 4-7 days following treatment ]Negative Test of Cure (i.e. Rectal gonorrhea culture) after treatment
- Tolerability of 2g Aztreonam IM [ Time Frame: Immediately following injection and 4-7 days following injection ]Subjects' self-report of injection related pain on a scale from 0 - 10
- Side Effects of 2g Aztreonam IM [ Time Frame: assessed immediately following injection and 4-7 days after injection ]Subject's report of perceived side effects related to study drug based on responses to standard side effect questionnaire.
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): NCT03867734
|United States, Washington|
|Public Health -- Seattle & King County STD Clinic|
|Seattle, Washington, United States, 98104|
|Principal Investigator:||Lindley Barbee, MD, MPH||University of Washington|