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

• ClinicalTrials.gov Identifier: NCT05971550
• Recruitment Status: Not yet recruiting
• First Posted: August 2, 2023
• Last Update Posted: August 2, 2023
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Neisseria Gonorrhoeae Infection; Asymptomatic Pharyngeal Carriage	Other: Absence of antibiotic treatment; Drug: Ceftriaxone	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 254 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Clearance of Asymptomatic Pharyngeal Carriage of Neisseria Gonorrhoeae With or Without Ceftriaxone Treatment: Randomized Non-inferiority Study
• Estimated Study Start Date: September 2023
• Estimated Primary Completion Date: December 2025
• Estimated Study Completion Date: December 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Proportion of patients with a negative pharyngeal nucleic acid amplification test (NAAT) for Neisseria gonorrhoeae (NG) [ Time Frame: 3 months after inclusion ]

Secondary Outcome Measures :

1. Proportion of patients with a negative pharyngeal nucleic acid amplification test (NAAT) and a negative pharyngeal culture for Neisseria gonorrhoeae (NG) [ Time Frame: at 1 month after inclusion ]
2. Proportion of patients with negative pharyngeal NG cultures [ Time Frame: at 3 months after inclusion ]
3. Proportion of patients carrying methicillin-resistant Staphylococcus aureus (MRSA) [ Time Frame: at 1 month after inclusion ]
   Impact of ceftriaxone on the carriage of methicillin-resistant Staphylococcus aureus (MRSA) on the pharyngeal sample
4. Proportion of patients carrying extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae [ Time Frame: at 1 month after inclusion ]
   Impact of ceftriaxone on the carriage of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae on the anal sample
5. Proportion of patients carrying methicillin-resistant Staphylococcus aureus (MRSA) [ Time Frame: at 3 months after inclusion ]
   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
6. Proportion of patients carrying extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae [ Time Frame: at 3 months after inclusion ]
   Impact of ceftriaxone on the carriage of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae on the anal sample
7. Proportion of patients with spontaneous pharyngeal clearance of NG [ Time Frame: at 1 month after inclusion ]

   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
8. Proportion of patients with spontaneous pharyngeal clearance of NG [ Time Frame: at 3 months after inclusion ]

   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
9. Proportion of partners with NAAT positive for NG [ Time Frame: At inclusion of the partner ]
   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)
10. Proportion of partners with NG cultures positive [ Time Frame: At inclusion of the partner ]
    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)
11. Proportion of partners with NAAT positive for NG [ Time Frame: at 1 month after inclusion of the partner ]
    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)
12. Proportion of partners with NG cultures positive [ Time Frame: at 1 month after inclusion of the partner ]
    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)
13. Proportion of partners with NAAT positive for NG [ Time Frame: at 3 months after inclusion of the partner ]
    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)
14. Proportion of partners with NG cultures positive [ Time Frame: at 3 months after inclusion of the partner ]
    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)
15. Proportion of identical genome between partner and patient [ Time Frame: Up to 3 months ]
16. Proportion of patients with Resistant NG strains [ Time Frame: Up to 3 months ]
17. Proportion of partners with Resistant NG strains [ Time Frame: Up to 3 months ]
18. Proportion of adverse events [ Time Frame: Up to 3 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Contacts

Contact: Claire Pintado, Dr; +33142494973; claire.pintado@aphp.fr

Contact: Jérôme Lambert, Dr; +33142499742; jerome.lambert@u-paris.fr

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

More Information

• Responsible Party: Assistance Publique - Hôpitaux de Paris
• ClinicalTrials.gov Identifier: NCT05971550
• Other Study ID Numbers: APHP210080
• First Posted: August 2, 2023
• Last Update Posted: August 2, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Gonorrhea; Neisseriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Sexually Transmitted Diseases, Bacterial; Sexually Transmitted Diseases; Communicable Diseases; Genital Diseases; Urogenital Diseases; Anti-Bacterial Agents; Ceftriaxone; Anti-Infective Agents; Third Generation Cephalosporins; Beta Lactam Antibiotics