Aztreonam for Pharyngeal Gonorrhea

NCT ID: NCT03867734

Last Updated: 2022-01-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-05
• Study Completion Date: 2019-09-30

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

Conditions

Gonorrhea of Pharynx; Gonorrhea

Study Design

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

Study Groups

2g Aztreonam

Subjects to receive 2g Aztreonam IM for the treatment of gonorrhea

Group Type: EXPERIMENTAL

Aztreonam

Intervention Type: DRUG

2g IM Aztreonam

Interventions

Aztreonam

2g IM Aztreonam

Intervention Type: DRUG

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

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Washington

OTHER

Sponsor Role: lead

Responsible Party

Lindley Barbee

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lindley 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, 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.

Reference Type: DERIVED

PMID: 33077658 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

STUDY00003878-02

Identifier Type: -

Identifier Source: org_study_id