Trial Comparing Ceftriaxone Plus Azithromycin Versus Ceftriaxone for the Treatment of Gonorrhea

Study Overview
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Brief Summary
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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.

Official Title
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An Open Label Randomized Controlled Trial Comparing the Effect of Ceftriaxone Plus Azithromycin Versus Ceftriaxone for the Treatment of Neisseria Gonorrhoeae on the Resistome

Conditions
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Neisseria Gonorrhoeae

Intervention / Treatment
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* Drug: Rocephin
* Drug: Azithromycin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Rocephine®<br>ceftriaxone 1g + lidocaine 35mg; intramuscular injection | Drug: Rocephin<br>* Single dose of Rocephine® (= ceftriaxone 1g + lidocaine 35mg) intramuscular injection<br>* Other names: Ceftriaxone;|
| Active Comparator: Rocephine® + Azithromycin<br>ceftriaxone 1g + lidocaine 35mg intramuscular injection + azithromycin 2g orally | Drug: Rocephin<br>* Single dose of Rocephine® (= ceftriaxone 1g + lidocaine 35mg) intramuscular injection<br>* Other names: Ceftriaxone;Drug: Azithromycin<br>* Single dose of Rocephine® (= ceftriaxone 1g + lidocaine 35mg) intramuscular injection + single dose of azithromycin 2g orally<br>* Other names: Zithromax;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 . | Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Day 14 | 
| 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 | Day 14 | 
| 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. | Day 14 | 
| 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 | Day 0 and Day 14 | 
| 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 | Day 14 |