Aztreonam for Pharyngeal Gonorrhea

NCT03867734 | Completed Phase 2 Results FDA Drug

• 1 other identifier: STUDY00003878-02
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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. 1.Determine the proportion of persons whose pharyngeal gonococcal infections are cured with a single dose of 2g aztreonam intramuscularly.
2. 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. 3.Evaluate the tolerability of 2g IM of aztreonam .
4. 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. 5.Among treatment failures, conduct exploratory analyses comparing pre- and post-treatment MIC for evidence of induced resistance.

Conditions

Gonorrhea of Pharynx; Gonorrhea

Keywords

aztreonam; treatment study

Outcome Measures

Primary Outcomes (1)

• 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

  Negative Test of Cure (i.e. Pharyngeal Gonorrhea Culture) after Treatment

  4-7 days following treatment

Secondary Outcomes (3)

• Efficacy of 2 g Aztreonam for N. Gonorrhoeae at Anogenital Sites

  Test of Cure 4-7 days following treatment

• Tolerability of 2g Aztreonam IM

  Immediately following injection

• Side Effects of 2g Aztreonam IM

  assessed immediately following injection and 4-7 days after injection

Study Arms (1)

2g Aztreonam

EXPERIMENTAL

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

Drug: Aztreonam

Interventions

Aztreonam DRUG

2g IM Aztreonam

2g Aztreonam

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Washington: lead

Study Sites (1)

Public Health -- Seattle & King County STD Clinic

Seattle, Washington, 98104, United States

Location

Related Publications (1)

• 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.

  PMID: 33077658 DERIVED

MeSH Terms

Conditions

Gonorrhea

Interventions

Aztreonam

Condition Hierarchy (Ancestors)

Neisseriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Sexually Transmitted Diseases, Bacterial; Sexually Transmitted Diseases; Communicable Diseases; Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Monobactams; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Lindley A. Barbee, MD, MPH
• Organization: University of Washington

lbarbee@uw.edu

206-744-2595

Study Officials

• Lindley Barbee, MD, MPH

  University of Washington

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Demonstration Study

Study Record Dates

• First Submitted: March 4, 2019
• First Posted: March 8, 2019
• Study Start: April 5, 2019
• Primary Completion: September 30, 2019
• Study Completion: September 30, 2019
• Last Updated: January 18, 2022
• Results First Posted: January 6, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)