Clinical trial NCT03867734: Aztreonam for Pharyngeal Gonorrhea
Official title: Aztreonam for Pharyngeal Gonorrhea: A Demonstration Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Gonorrhea of Pharynx
Gonorrhea
Keywords: aztreonam
treatment study
Lead sponsor: University of Washington
Sponsor class: OTHER
First posted: 2019-03-08
Enrollment: 32
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Demonstration Study
Primary purpose: TREATMENT

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 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.

Objectives:

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:

1. Determine the proportion of persons whose pharyngeal gonococcal infections are cured with a single dose of 2g aztreonam intramuscularly.
2. Determine the proportion of persons with urethral and/or rectal gonorrhea whose infections are cured with a single dose of 2g aztreonam IM.
3. Evaluate the tolerability of 2g IM of aztreonam .
4. 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.
5. 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


Eligibility criteria: Inclusion Criteria:

* Persons diagnosed with pharyngeal gonorrhea or gonococcal urethritis who are undergoing pharyngeal gonorrhea testing, who are not yet treated.

Exclusion Criteria:

* Age less than 16 years
* Receipt of antibiotics in ≤30 days
* Known allergy to aztreonam
* History of renal disease (including diagnosis of solitary kidney, chronic renal insufficiency, renal cell carcinoma etc.)
* 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

Primary outcomes:
measure: 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
timeFrame: 4-7 days following treatment
Secondary outcomes:
measure: Efficacy of 2 g Aztreonam for N. Gonorrhoeae at Anogenital Sites
timeFrame: Test of Cure 4-7 days following treatment
measure: Tolerability of 2g Aztreonam IM
timeFrame: Immediately following injection
measure: Side Effects of 2g Aztreonam IM
timeFrame: assessed immediately following injection and 4-7 days after injection
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Public Health -- Seattle & King County STD Clinic
state: Washington
Study officials:
affiliation: University of Washington
name: Lindley Barbee, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Barbee LA, Soge OO, Ocbamichael N, LeClair A, Golden MR. Single-Arm Open-Label Clinical Trial of Two Grams of Aztreonam for the Treatment of Neisseria gonorrhoeae. Antimicrob Agents Chemother. 2020 Dec 16;65(1):e01739-20. doi: 10.1128/AAC.01739-20. Print 2020 Dec 16.