Trial Comparing Ceftriaxone Plus Azithromycin Versus Ceftriaxone for the Treatment of Gonorrhea (ResistAZM)

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

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.

Study Overview

• Status: Completed
• Conditions: Neisseria Gonorrhoeae
• Intervention / Treatment: Drug: Rocephin; Drug: Azithromycin

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen, Belgium, 2000
    • Institute of Tropical Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

1. Able and willing to provide written informed consent
2. Male sex at birth
3. At least 18 years old
4. 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:

1. Use of any macrolide antibiotics (azithromycin, clarithromycin, erythromycin, roxithromycin, spiramycin) in previous 6 months
2. Known contra-indications or allergy to ceftriaxone, azithromycin or lidocaine
3. 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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
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

Collaborators and Investigators

• Sponsor: Institute of Tropical Medicine, Belgium

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2022
• Primary Completion (Actual): May 9, 2022
• Study Completion (Actual): May 9, 2022

Study Registration Dates

• First Submitted: July 20, 2021
• First Submitted That Met QC Criteria: August 24, 2021
• First Posted (Actual): August 30, 2021

Study Record Updates

• Last Update Posted (Actual): August 2, 2024
• Last Update Submitted That Met QC Criteria: February 15, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Communicable Diseases; Sexually Transmitted Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Neisseriaceae Infections; Sexually Transmitted Diseases, Bacterial; Urogenital Diseases; Genital Diseases; Gonorrhea; Anti-Infective Agents; Anti-Bacterial Agents; Third Generation Cephalosporins; Beta Lactam Antibiotics; Ceftriaxone; Azithromycin
• Other Study ID Numbers: ITM202101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No