Trial Comparing Ceftriaxone Plus Azithromycin Versus Ceftriaxone for the Treatment of Gonorrhea (ResistAZM)
Primary Purpose
Neisseria Gonorrhoeae
Status
Completed
Phase
Phase 4
Locations
Belgium
Study Type
Interventional
Intervention
Rocephin
Azithromycin
Sponsored by
About this trial
This is an interventional supportive care trial for Neisseria Gonorrhoeae
Eligibility Criteria
Inclusion criteria:
- Able and willing to provide written informed consent
- Male sex at birth
- At least 18 years old
- Confirmed diagnosis of urethritis, proctitis or pharyngitis N. gonnorrhea - symptomatic or asymptomatic (Diagnosis of N. gonnorrhea will be by a positive NAAT performed according to the ITMs current laboratory protocols or for patients with urethritis a positive gram/methylene blue stain)
Exclusion criteria:
- Use of any macrolide antibiotics (azithromycin, clarithromycin, erythromycin, roxithromycin, spiramycin) in previous 6 months
- Known contra-indications or allergy to ceftriaxone, azithromycin or lidocaine
- Presence of any other condition, including other Sexually Transmitted Infections that will (likely) require the administration of another antibiotic at the time of enrollment, as assessed by the treating physician
Sites / Locations
- Institute of Tropical Medicine
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Rocephine®
Rocephine® + Azithromycin
Arm Description
ceftriaxone 1g + lidocaine 35mg; intramuscular injection
ceftriaxone 1g + lidocaine 35mg intramuscular injection + azithromycin 2g orally
Outcomes
Primary Outcome Measures
Macrolide resistance determinants
During the bioinformatic analyses, each identified antibiotic-resistance determinant will be categorized at the class level using a read-based classification tool. The primary outcome will be the ratio of mean macrolide resistance determinants in the day 14 anorectal samples between the two treatment groups. This ratio will be calculated by dividing the mean normalized read count of macrolide- resistance determinants categorized at the class level in the Ceftriaxone/Azithromycin group by the corresponding mean quantity in the Ceftriaxone group .
Secondary Outcome Measures
Read count of resistance determinants for each non-macrolide antibiotic class
The ratio of mean normalized read count of resistance determinants for each non-macrolide antibiotic class in the day 14 anorectal samples between the two treatment groups
Read count of resistance determinants for each macrolide and non-macrolide antibiotic class
The ratio of mean normalized read count of resistance determinants for each macrolide and non-macrolide antibiotic class in the day 14 oropharyngeal samples between the two treatment groups
Proportion of oropharyngeal commensal Neisseria that are macrolide resistant
The difference in proportion of oropharyngeal commensal Neisseria that are macrolide resistant between the two treatment groups at day 14. For each individual the proportion of oropharyngeal commensal Neisseria that are macrolide resistant will be calculated by dividing the number of macrolide-resistant colonies of commensal Neisseria grown on modified LB agar-azithromycin-1mg/L by the total number of commensal Neisseria colonies grown on modified LB agar without Azithromycin.
Acquisition of phenotypic resistance to Azythromycin by N. gonnorrhea
The difference in time until acquisition of phenotypic resistance to Azithromycin by N. gonnorrhea in the morbidostat upon exposure to commensal Neisseria DNA extracts from each treatment group
Diameter of the inhibition zone of N gonnorrhea
The difference in diameter of the inhibition zone of N. gonnorrhea during agar overlay experiments using oropharyngeal commensal Neisseria and Streptococci from day 14 samples from each treatment group
Full Information
NCT ID
NCT05027516
First Posted
July 20, 2021
Last Updated
March 24, 2023
Sponsor
Institute of Tropical Medicine, Belgium
1. Study Identification
Unique Protocol Identification Number
NCT05027516
Brief Title
Trial Comparing Ceftriaxone Plus Azithromycin Versus Ceftriaxone for the Treatment of Gonorrhea
Acronym
ResistAZM
Official Title
An Open Label Randomized Controlled Trial Comparing the Effect of Ceftriaxone Plus Azithromycin Versus Ceftriaxone for the Treatment of Neisseria Gonorrhoeae on the Resistome
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
January 17, 2022 (Actual)
Primary Completion Date
May 9, 2022 (Actual)
Study Completion Date
May 9, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institute of Tropical Medicine, Belgium
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
In this Randomized Controlled Trial, the investigators will recruit 42 men attending the STI and HIV clinic at the Institute of Tropical Medicine, with a diagnosis of N. gonorrhoeae and randomize them 1:1 to receive either ceftriaxone or ceftriaxone/azithromycin. They will be followed-up for a test of cure visit at day 14 post-treatment where urine, oropharyngeal and anorectal samples will be taken to test for cure and monitor treatment effects on the microbiome and resistome. The primary outcome will be evaluating the difference in the abundance of resistance conferring genes in the rectal microbiome in the two arms, 14 days after the receipt of therapy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neisseria Gonorrhoeae
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
42 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Rocephine®
Arm Type
Active Comparator
Arm Description
ceftriaxone 1g + lidocaine 35mg; intramuscular injection
Arm Title
Rocephine® + Azithromycin
Arm Type
Active Comparator
Arm Description
ceftriaxone 1g + lidocaine 35mg intramuscular injection + azithromycin 2g orally
Intervention Type
Drug
Intervention Name(s)
Rocephin
Other Intervention Name(s)
Ceftriaxone
Intervention Description
Single dose of Rocephine® (= ceftriaxone 1g + lidocaine 35mg) intramuscular injection
Intervention Type
Drug
Intervention Name(s)
Azithromycin
Other Intervention Name(s)
Zithromax
Intervention Description
Single dose of Rocephine® (= ceftriaxone 1g + lidocaine 35mg) intramuscular injection + single dose of azithromycin 2g orally
Primary Outcome Measure Information:
Title
Macrolide resistance determinants
Description
During the bioinformatic analyses, each identified antibiotic-resistance determinant will be categorized at the class level using a read-based classification tool. The primary outcome will be the ratio of mean macrolide resistance determinants in the day 14 anorectal samples between the two treatment groups. This ratio will be calculated by dividing the mean normalized read count of macrolide- resistance determinants categorized at the class level in the Ceftriaxone/Azithromycin group by the corresponding mean quantity in the Ceftriaxone group .
Time Frame
Day 14
Secondary Outcome Measure Information:
Title
Read count of resistance determinants for each non-macrolide antibiotic class
Description
The ratio of mean normalized read count of resistance determinants for each non-macrolide antibiotic class in the day 14 anorectal samples between the two treatment groups
Time Frame
Day 14
Title
Read count of resistance determinants for each macrolide and non-macrolide antibiotic class
Description
The ratio of mean normalized read count of resistance determinants for each macrolide and non-macrolide antibiotic class in the day 14 oropharyngeal samples between the two treatment groups
Time Frame
Day 14
Title
Proportion of oropharyngeal commensal Neisseria that are macrolide resistant
Description
The difference in proportion of oropharyngeal commensal Neisseria that are macrolide resistant between the two treatment groups at day 14. For each individual the proportion of oropharyngeal commensal Neisseria that are macrolide resistant will be calculated by dividing the number of macrolide-resistant colonies of commensal Neisseria grown on modified LB agar-azithromycin-1mg/L by the total number of commensal Neisseria colonies grown on modified LB agar without Azithromycin.
Time Frame
Day 14
Title
Acquisition of phenotypic resistance to Azythromycin by N. gonnorrhea
Description
The difference in time until acquisition of phenotypic resistance to Azithromycin by N. gonnorrhea in the morbidostat upon exposure to commensal Neisseria DNA extracts from each treatment group
Time Frame
Day 0 and Day 14
Title
Diameter of the inhibition zone of N gonnorrhea
Description
The difference in diameter of the inhibition zone of N. gonnorrhea during agar overlay experiments using oropharyngeal commensal Neisseria and Streptococci from day 14 samples from each treatment group
Time Frame
Day 14
10. Eligibility
Sex
Male
Gender Based
Yes
Gender Eligibility Description
Inclusion of male sex at birth
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
Able and willing to provide written informed consent
Male sex at birth
At least 18 years old
Confirmed diagnosis of urethritis, proctitis or pharyngitis N. gonnorrhea - symptomatic or asymptomatic (Diagnosis of N. gonnorrhea will be by a positive NAAT performed according to the ITMs current laboratory protocols or for patients with urethritis a positive gram/methylene blue stain)
Exclusion criteria:
Use of any macrolide antibiotics (azithromycin, clarithromycin, erythromycin, roxithromycin, spiramycin) in previous 6 months
Known contra-indications or allergy to ceftriaxone, azithromycin or lidocaine
Presence of any other condition, including other Sexually Transmitted Infections that will (likely) require the administration of another antibiotic at the time of enrollment, as assessed by the treating physician
Facility Information:
Facility Name
Institute of Tropical Medicine
City
Antwerpen
ZIP/Postal Code
2000
Country
Belgium
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Trial Comparing Ceftriaxone Plus Azithromycin Versus Ceftriaxone for the Treatment of Gonorrhea
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