Clearance of Asymptomatic Pharyngeal Carriage of Neisseria Gonorrhoeae With or Without Ceftriaxone Treatment: Randomized Non-inferiority Study (PORTAPHAR)

Since the use of antibiotics, Neisseria Gonorrhoeae (NG) has acquired progressive resistance to penicillins, sulfonamides, tetracyclines and quinolones. The oropharynx is recognized as an important site for DNA exchange between NG and other commensal Neisseria, allowing NG to acquire new antimicrobial resistance. Despite the worrying data on the emergence of resistant NG, the recommendations remain to systematically treat these infections with ceftriaxone, including asymptomatic pharyngeal localizations. The objective of our study is to evaluate a ceftriaxone sparing strategy in order to limit the emergence of antibiotic resistance.

The primary objective of the study is to evaluate the clearance of Neisseria gonorrhoeae, 3 months after the diagnosis of asymptomatic pharyngeal carriage documented on nucleic acid amplification test (NAAT).

Study Overview

• Status: Not yet recruiting
• Conditions: Neisseria Gonorrhoeae Infection; Asymptomatic Pharyngeal Carriage
• Intervention / Treatment: Other: Absence of antibiotic treatment; Drug: Ceftriaxone

Detailed Description

Non-inferiority, multicenter, prospective, randomized open-label study, in two parallel arms, comparing the pharyngeal clearance of Neisseria gonorrhoeae (NG) at 3 months with or without treatment with ceftriaxone.

Experimental group: Absence of antibiotic treatment for at most 3 months after screening for asymptomatic NG pharyngeal infection (treatment if onset of symptoms related to Sexually Transmitted Infection or positive Polymerase chain reaction (PCR) at 3 months)

Control group: Ceftriaxone 1000 mg by parenteral intramuscular route, in a single dose, according to the national recommendations in force, to be repeated if pharyngeal Polymerase chain reaction (PCR) again positive for NG during follow-up.

• Study Type: Interventional
• Enrollment (Estimated): 254
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jérôme Lambert, Dr; Phone Number: +33142499742; Email: jerome.lambert@u-paris.fr
• Study Contact Backup: Name: Claire Pintado, Dr; Phone Number: +33142494973; Email: claire.pintado@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Patients (n=154):

Patient inclusion criteria :

• Adult patient (age ≥ 18 years old)

• Patient consulting for a pharyngeal Neisseria gonorrhoeae Sexually Transmitted Infection (STI) and meeting the following criteria :

  • Positive sample for NAAT by PCR in the pharynx for Neisseria gonorrhoeae dating back a maximum of 7 days (the date of the sample and those of inclusion will be compared) and
  • asymptomatic patient
• Absence of symptoms of other bacterial STIs or other asymptomatic bacterial STIs confirmed on the systematic screening assessment carried out within 7 days before inclusion
• Patient's agreement to use protection or abstinence from all oral sex for 3 months follow-up (experimental group) or for 7 days (control group)
• For men whose female partner(s) are of childbearing age and for women of childbearing age: use of effective contraception (failure rate less than 1% per year) throughout research
• Patient benefiting from a social health security scheme
• Patient having signed a free and informed consent

Patients non-inclusion criteria :

• Minor patient
• Symptomatic patient in the pharynx
• Presence of symptoms of another bacterial STI or of an asymptomatic bacterial STI confirmed on the screening report carried out within 7 days before inclusion
• Antibiotic treatment that may be active on Neisseria gonorrhoeae (C3G, Fluoroquinolones, Macrolides, Cyclins, Aminosides, Penicillins) within 14 days before inclusion
• Hypersensitivity to ceftriaxone, other cephalosporins or to any of the excipients
• History of severe hypersensitivity (e.g. anaphylactic reaction) to another class of antibacterial agents of the beta-lactam family (penicillins, monobactams and carbapenems).
• Contraindication to ceftriaxone
• Contraindication to intramuscular injections
• Person under legal protection, under guardianship or curatorship, person deprived of liberty, under safeguard of justice, subject to psychiatric care, under duress, admitted to a health or social establishment for purposes other than those of research
• Pregnant or breastfeeding woman
• Lack of social health insurance
• Patient included in another interventional study

Partners (n=100) :

Partner Inclusion Criteria :

• Sexual contact of the index case (genito-anal or genito-vaginal, oro-genital or oro-anal or oro-oral relations) in the month preceding the inclusion of the index case
• Adult patient (age ≥ 18 years old)
• Patient benefiting from a social health security scheme
• Patient having signed a free and informed consent

Partner non-inclusion Criteria:

• Minor patient
• Person under legal protection, under guardianship or curatorship, person deprived of liberty, under safeguard of justice, subject to psychiatric care, under duress, admitted to a health or social establishment for purposes other than those of research
• Patient included in another interventional study
• Pregnant or breastfeeding woman

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients : Absence of antibiotic treatment	Other: Absence of antibiotic treatment; Absence of antibiotic treatment for at most 3 months after screening for asymptomatic NG pharyngeal infection (treatment if onset of symptoms related to STI or positive PCR at 3 months)
Active Comparator: Patients : Ceftriaxone	Drug: Ceftriaxone; Ceftriaxone 1000 mg by parenteral intramuscular route, in a single dose, according to the national recommendations in force, to be repeated if pharyngeal PCR again positive for NG during follow-up

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients with a negative pharyngeal nucleic acid amplification test (NAAT) for Neisseria gonorrhoeae (NG)	3 months after inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with a negative pharyngeal nucleic acid amplification test (NAAT) and a negative pharyngeal culture for Neisseria gonorrhoeae (NG)		at 1 month after inclusion
Proportion of patients with negative pharyngeal NG cultures		at 3 months after inclusion
Proportion of patients carrying methicillin-resistant Staphylococcus aureus (MRSA)	Impact of ceftriaxone on the carriage of methicillin-resistant Staphylococcus aureus (MRSA) on the pharyngeal sample	at 1 month after inclusion
Proportion of patients carrying extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae	Impact of ceftriaxone on the carriage of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae on the anal sample	at 1 month after inclusion
Proportion of patients carrying methicillin-resistant Staphylococcus aureus (MRSA)	Impact of ceftriaxone on the carriage of methicillin-resistant Staphylococcus aureus (MRSA) on the pharyngeal sample and extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae on the anal sample	at 3 months after inclusion
Proportion of patients carrying extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae	Impact of ceftriaxone on the carriage of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae on the anal sample	at 3 months after inclusion
Proportion of patients with spontaneous pharyngeal clearance of NG	Analysis of factors associated with spontaneous pharyngeal clearance of NG : Socio-demographic and behavioural characteristics; Amount of NG in the pharynx assessed by exploratory semi-quantitative PCR; Bactericidal activity of anti-gonococcal antibodies and the production of specific anti-gonococcal antibodies in pharyngeal secretions	at 1 month after inclusion
Proportion of patients with spontaneous pharyngeal clearance of NG	Analysis of the factors associated with spontaneous pharyngeal clearance of NG : Socio-demographic and behavioural characteristics; Amount of NG in the pharynx assessed by exploratory semi-quantitative PCR; Bactericidal activity of anti-gonococcal antibodies and the production of specific anti-gonococcal antibodies in pharyngeal secretions	at 3 months after inclusion
Proportion of partners with NAAT positive for NG	Proportion of partners with NAAT positive for NG on at least one of the three sites of infection (pharyngeal, anal, first-void urine or vaginal self-sampling)	At inclusion of the partner
Proportion of partners with NG cultures positive	Proportion of partners with NG cultures positive on at least one of the three sites of infection (pharyngeal, anal, first-void urine or vaginal self-sampling)	At inclusion of the partner
Proportion of partners with NAAT positive for NG	Proportion of partners with NAAT positive for NG on at least one of the three sites of infection (pharyngeal, anal, first-void urine or vaginal self-sampling)	at 1 month after inclusion of the partner
Proportion of partners with NG cultures positive	Proportion of partners with NG cultures positive on at least one of the three sites of infection (pharyngeal, anal, first-void urine or vaginal self-sampling)	at 1 month after inclusion of the partner
Proportion of partners with NAAT positive for NG	Proportion of partners with NAAT positive for NG on at least one of the three sites of infection (pharyngeal, anal, first-void urine or vaginal self-sampling)	at 3 months after inclusion of the partner
Proportion of partners with NG cultures positive	Proportion of partners with NG cultures positive on at least one of the three sites of infection (pharyngeal, anal, first-void urine or vaginal self-sampling)	at 3 months after inclusion of the partner
Proportion of identical genome between partner and patient		Up to 3 months
Proportion of patients with Resistant NG strains		Up to 3 months
Proportion of partners with Resistant NG strains		Up to 3 months
Proportion of adverse events		Up to 3 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2023
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: April 14, 2023
• First Submitted That Met QC Criteria: July 24, 2023
• First Posted (Actual): August 2, 2023

Study Record Updates

• Last Update Posted (Actual): August 2, 2023
• Last Update Submitted That Met QC Criteria: July 24, 2023
• Last Verified: February 1, 2023

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; Ceftriaxone; Anti-Bacterial Agents
• Other Study ID Numbers: APHP210080

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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