Trial Outcomes & Findings for Trial Comparing Ceftriaxone Plus Azithromycin Versus Ceftriaxone for the Treatment of Gonorrhea (NCT NCT05027516)

Last Updated: 2024-08-02

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

42 participants

Primary outcome timeframe

Day 14

Results posted on

2024-08-02

Participant Flow

Participant milestones

Participant milestones
Measure	Rocephine® ceftriaxone 1g + lidocaine 35mg; intramuscular injection Rocephin: Single dose of Rocephine® (= ceftriaxone 1g + lidocaine 35mg) intramuscular injection	Rocephine® + Azithromycin ceftriaxone 1g + lidocaine 35mg intramuscular injection + azithromycin 2g orally Rocephin: Single dose of Rocephine® (= ceftriaxone 1g + lidocaine 35mg) intramuscular injection Azithromycin: Single dose of Rocephine® (= ceftriaxone 1g + lidocaine 35mg) intramuscular injection + single dose of azithromycin 2g orally
Overall Study STARTED	22	20
Overall Study COMPLETED	22	20
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rocephine® n=22 Participants ceftriaxone 1g + lidocaine 35mg; intramuscular injection Rocephin: Single dose of Rocephine® (= ceftriaxone 1g + lidocaine 35mg) intramuscular injection	Rocephine® + Azithromycin n=20 Participants ceftriaxone 1g + lidocaine 35mg intramuscular injection + azithromycin 2g orally Rocephin: Single dose of Rocephine® (= ceftriaxone 1g + lidocaine 35mg) intramuscular injection Azithromycin: Single dose of Rocephine® (= ceftriaxone 1g + lidocaine 35mg) intramuscular injection + single dose of azithromycin 2g orally	Total n=42 Participants Total of all reporting groups
Age, Continuous	40 years n=22 Participants	41.5 years n=20 Participants	40 years n=42 Participants
Sex/Gender, Customized Male sex at birth	22 participants n=22 Participants	20 participants n=20 Participants	0 participants n=42 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
HIV status: Positive	5 Participants n=22 Participants	4 Participants n=20 Participants	9 Participants n=42 Participants
HIV status: Negative	17 Participants n=22 Participants	16 Participants n=20 Participants	33 Participants n=42 Participants
Symptomatic NG	7 Participants n=22 Participants	6 Participants n=20 Participants	13 Participants n=42 Participants
Number of partners (last 3 months)	5 partners n=22 Participants	5 partners n=20 Participants	5 partners n=42 Participants
Use of antibiotics in the last 12 months	8 Participants n=22 Participants	10 Participants n=20 Participants	18 Participants n=42 Participants
Amoxicillin/Clavulanic acid	0 Participants n=22 Participants	2 Participants n=20 Participants	2 Participants n=42 Participants
Ceftriaxone	0 Participants n=22 Participants	0 Participants n=20 Participants	0 Participants n=42 Participants
Doxycycline	0 Participants n=22 Participants	0 Participants n=20 Participants	0 Participants n=42 Participants
Penicillin	0 Participants n=22 Participants	0 Participants n=20 Participants	0 Participants n=42 Participants
PrEP use	14 Participants n=22 Participants	13 Participants n=20 Participants	27 Participants n=42 Participants
Infection site: Anorectal	2 Participants n=22 Participants	1 Participants n=20 Participants	3 Participants n=42 Participants
Infection site: Urethral	4 Participants n=22 Participants	5 Participants n=20 Participants	9 Participants n=42 Participants
Infection site: Pooled	16 Participants n=22 Participants	14 Participants n=20 Participants	30 Participants n=42 Participants
Teeth discoloration	0 Participants n=22 Participants	0 Participants n=20 Participants	0 Participants n=42 Participants
Dental caries	0 Participants n=22 Participants	0 Participants n=20 Participants	0 Participants n=42 Participants

PRIMARY outcome

Timeframe: Day 14

Population: The primary analysis of assessing the ratio between the mean normalized read count of macrolide resistance determinants in anorectal microbiome between the two groups was done using permutation test with 10 000 permutations.

Outcome measures

Outcome measures
Measure	Rocephine n=22 Participants Ceftriaxone 1g + lidocaine 35mg intramuscular injection on day 0	Azithromycin / Rocephine® n=20 Participants ceftriaxone 1g + lidocaine 35mg intramuscular injection on day 0 azithromycin 2g per os on day 0
Macrolide Resistance Determinants	110.3 normalized determinants/million reads Interval 64.54 to 156.06	167.53 normalized determinants/million reads Interval 97.86 to 237.19

SECONDARY outcome

Timeframe: Day 14

Population: The normalized macrolide resistance determinants were calculated by dividing the number of macrolide resistance reads by the total number of bacterial reads. The resulting proportion was then multiplied by 106 to present results in normalized determinants per million reads. No sample had a total number of reads below 95 thousand.

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

Outcome measures

Outcome measures
Measure	Rocephine n=22 Participants Ceftriaxone 1g + lidocaine 35mg intramuscular injection on day 0	Azithromycin / Rocephine® n=20 Participants ceftriaxone 1g + lidocaine 35mg intramuscular injection on day 0 azithromycin 2g per os on day 0
Read Count of Resistance Determinants for Each Non-macrolide Antibiotic Class Aminoglycosides	34.41 normalized determinants/million reads Interval 11.36 to 57.45	22.22 normalized determinants/million reads Interval 14.98 to 29.46
Read Count of Resistance Determinants for Each Non-macrolide Antibiotic Class Betalactams	110.46 normalized determinants/million reads Interval 80.17 to 140.76	89.82 normalized determinants/million reads Interval 68.36 to 111.28
Read Count of Resistance Determinants for Each Non-macrolide Antibiotic Class Bacitracin	4.63 normalized determinants/million reads Interval 0.0 to 11.21	1.11 normalized determinants/million reads Interval 0.0 to 2.96
Read Count of Resistance Determinants for Each Non-macrolide Antibiotic Class Glycopeptides	0.26 normalized determinants/million reads Interval 0.0 to 0.77	0.14 normalized determinants/million reads Interval 0.0 to 0.4
Read Count of Resistance Determinants for Each Non-macrolide Antibiotic Class Trimethoprim	2.73 normalized determinants/million reads Interval 0.7 to 4.77	1.55 normalized determinants/million reads Interval 0.4 to 2.69
Read Count of Resistance Determinants for Each Non-macrolide Antibiotic Class Cationic antimicrobial peptides	16.52 normalized determinants/million reads Interval 0.0 to 38.45	5.52 normalized determinants/million reads Interval 0.0 to 14.65
Read Count of Resistance Determinants for Each Non-macrolide Antibiotic Class Mupirocin	0.84 normalized determinants/million reads Interval 0.0 to 1.86	0 normalized determinants/million reads Interval 0.0 to 0.0
Read Count of Resistance Determinants for Each Non-macrolide Antibiotic Class Metronidazole	0.2 normalized determinants/million reads Interval 0.0 to 0.61	0.06 normalized determinants/million reads Interval 0.0 to 0.19
Read Count of Resistance Determinants for Each Non-macrolide Antibiotic Class Fluoroquinolones	9.44 normalized determinants/million reads Interval 0.0 to 21.97	23.9 normalized determinants/million reads Interval 0.0 to 68.13
Read Count of Resistance Determinants for Each Non-macrolide Antibiotic Class Sulfonamides	5.47 normalized determinants/million reads Interval 0.0 to 11.84	0.62 normalized determinants/million reads Interval 0.0 to 1.76
Read Count of Resistance Determinants for Each Non-macrolide Antibiotic Class Tetracyclines	348.12 normalized determinants/million reads Interval 286.41 to 409.82	423.8 normalized determinants/million reads Interval 361.52 to 486.09

SECONDARY outcome

Timeframe: Day 0 and Day 14

Population: change of proportion of isolates resistant to azithromycin between day 0 and day 14

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

Outcome measures

Outcome measures
Measure	Rocephine n=22 Participants Ceftriaxone 1g + lidocaine 35mg intramuscular injection on day 0	Azithromycin / Rocephine® n=20 Participants ceftriaxone 1g + lidocaine 35mg intramuscular injection on day 0 azithromycin 2g per os on day 0
Acquisition of Phenotypic Resistance to Azythromycin by N. Gonnorrhea Streptococci day 0	0.649 Proportion of isolates resistant to AZM	0.669 Proportion of isolates resistant to AZM
Acquisition of Phenotypic Resistance to Azythromycin by N. Gonnorrhea Streptococci day 14	0.572 Proportion of isolates resistant to AZM	0.739 Proportion of isolates resistant to AZM
Acquisition of Phenotypic Resistance to Azythromycin by N. Gonnorrhea Commensal Neisseria day 0	0.534 Proportion of isolates resistant to AZM	0.471 Proportion of isolates resistant to AZM
Acquisition of Phenotypic Resistance to Azythromycin by N. Gonnorrhea Commensal Neisseria day 14	0.542 Proportion of isolates resistant to AZM	0.638 Proportion of isolates resistant to AZM

Adverse Events

Rocephine®

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Rocephine® + Azithromycin

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Rocephine® n=22 participants at risk ceftriaxone 1g + lidocaine 35mg; intramuscular injection Rocephin: Single dose of Rocephine® (= ceftriaxone 1g + lidocaine 35mg) intramuscular injection	Rocephine® + Azithromycin n=20 participants at risk ceftriaxone 1g + lidocaine 35mg intramuscular injection + azithromycin 2g orally Rocephin: Single dose of Rocephine® (= ceftriaxone 1g + lidocaine 35mg) intramuscular injection Azithromycin: Single dose of Rocephine® (= ceftriaxone 1g + lidocaine 35mg) intramuscular injection + single dose of azithromycin 2g orally
Gastrointestinal disorders abdominal pain	0.00% 0/22 • Adverse events and serious adverse events were collected over the whole study duration (4 months).	5.0% 1/20 • Number of events 1 • Adverse events and serious adverse events were collected over the whole study duration (4 months).
Gastrointestinal disorders nausea	0.00% 0/22 • Adverse events and serious adverse events were collected over the whole study duration (4 months).	15.0% 3/20 • Number of events 3 • Adverse events and serious adverse events were collected over the whole study duration (4 months).
General disorders pain at injection site	9.1% 2/22 • Number of events 2 • Adverse events and serious adverse events were collected over the whole study duration (4 months).	5.0% 1/20 • Number of events 1 • Adverse events and serious adverse events were collected over the whole study duration (4 months).
Nervous system disorders presyncope	0.00% 0/22 • Adverse events and serious adverse events were collected over the whole study duration (4 months).	5.0% 1/20 • Number of events 1 • Adverse events and serious adverse events were collected over the whole study duration (4 months).

Additional Information

Dr. Chris Kenyon

Institute of Tropical Medicine Antwerp

Phone: +32(0)32470786

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place