Doxycycline, Lymphogranuloma Venereum, no Anorectal Symptoms
Conditions
Keywords
Lymphogranuloma venereum, Chlamydia trachomatis, asymptomatic, doxycycline
Brief summary
Lymphogranuloma venereum (LGV) is a sexually transmitted infection (STI) caused by the L genotypes of C. trachomatis. Proctitis is the main clinical manifestation of infection in the current LGV epidemic. However, recent European studies reported that about 25% of the anal LGV infections are asymptomatic. In France, asymptomatic anal LGV increased from 36.1% (44/124) in 2020 to 52.4% (66/126) in 2022. LGV testing is recommended on all C. trachomatis-positive anorectal specimens because therapy of extended duration is required. Patients with anal C. trachomatis infection should be treated initially with 7-day course of doxycycline (200 mg per day orally) while awaiting the results of LGV testing. Treatment should be extended to 21 days in cases of LGV according to current European and USA guidelines for LGV treatment. This regimen is indicated for symptomatic and asymptomatic anorectal LGV, with a 98.5% treatment efficacy. However, there is no obvious biological basis for prolonged treatment of asymptomatic LGV. Three recent retrospective studies showed that a 7-day course of doxycycline was effective for the treatment of asymptomatic LGV, with microbial cure ranging from 97% (38/39) to 100% (54/54). The objective of this study is to evaluate the efficacy (microbiological cure rate) of a 7-day course of doxycycline 200 mg daily orally for the treatment of asymptomatic anal LGV infection, four weeks after treatment initiation.
Detailed description
Lymphogranuloma venereum (LGV) is a sexually transmitted infection (STI) caused by the L genotypes of C. trachomatis. LGV have reemerged in Europe, primarily in men who have sex with men (MSM). The number of LGV cases reported has risen year on year, from 739 in 2011 to 3124 in 2019 in European countries. Proctitis is the main clinical manifestation of infection in the current LGV epidemic. Recent European studies reported that about 25% of the anal LGV infections are asymptomatic. In France, asymptomatic anal LGV increased from 36.1% (44/124) in 2020 to 52.4% (66/126) in 2022. Guidelines on the management of LGV recommended that all MSM with anorectal C. trachomatis-positive specimens should be tested for LGV irrespective of symptoms. However, access to routine LGV testing is inconsistent in France and other European countries, and specimens need to be referred to expert laboratories with substantial additional cost and significant delay to receiving results. LGV testing is recommended because therapy of extended duration is required. Patients with anal C. trachomatis infection should be treated initially with 7-day course of doxycycline (200 mg per day orally) while awaiting the results of LGV testing. Treatment should be extended to 21 days in cases of LGV according to current European and USA guidelines for LGV treatment. This regimen is indicated for symptomatic and asymptomatic anorectal LGV, with a 98.5% treatment efficacy. However, there is no obvious biological basis for prolonged treatment of asymptomatic LGV. Three recent retrospective studies showed that a 7-day course of doxycycline was effective for the treatment of asymptomatic LGV, with microbial cure ranging from 97% (38/39) to 100% (54/54). These results suggest that a shorter course of doxycycline could be sufficient for treating asymptomatic anal LGV. In this study, subjects without anorectal symptoms and with anal specimens positive for LGV will be treated by a 7-day course of doxycycline 200 mg daily orally. The microbiological cure will be estimated four weeks after treatment initiation, with a self-collected anal specimen for the detection of LGV
Interventions
DRUGDoxycline
Doxycycline 200 mg daily orally for seven days
Sponsors
University Hospital, Bordeaux
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Male sex at birth * LGV-positive result on anal specimen using Nucleic Acid Amplification Test at screening * Having taken at least doxycycline for two days (i.e 400 mg of doxycycline) * Not having taken more than 7 days of doxycycline 200 mg per day * No more than 12 days between the date of sampling and date of inclusion * No anorectal symptoms * Individual available for participation and follow-up during the four weeks required for the study * Affiliate or beneficiary of a social security scheme * Free written informed consent signed by the participant or by a legal representative (in the event of the participant's inability to consent) and the investigator (no later than the day of inclusion and before any examination required by the research).
Exclusion criteria
* Individual with anorectal symptoms * Antibiotic treatment with antichlamydial activity (fluoroquinolones, macrolides-lincosamides-streptogramins, tetracyclines and rifampicin) within 28 days before the screening visit * Use of doxycycline post-exposure prophylaxis (Doxy-PEP) * Participation in another study * Individual under a measure of legal protection measure (safeguard of justice, guardianship or curatorship) or unable to consent * Refusal to participate in the study * Mental state rendering the person giving consent incapable of understanding the entirety of the trial * Participant detained by judicial or administrative decision. * Individual receiving an anticoagulant therapy * Individual with a history of known hypersensitivity to doxycycline or any other antibiotic of the tetracycline family or allergy to any of the excipients (Hydrogenated castor oil, povidone, anhydrous colloidal silica, magnesium stearate, microcrystalline cellulose, sodium carboxymethyl starch (type A)). * Individual treated with retinoids by general route. * Individual receiving 10,000 IU of vitamin A per day or more * Individual being a relative of the investigator or a relative of someone from the team directly involved in the trial, including assistant doctors, pharmacists, nurses, and trial coordinators
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Microbiological cure rate of a 7-day course of doxycycline for asymptomatic anal LGV | 4 weeks after treatment initiation | The microbiological cure is defined as a LGV-negative NAAT (Nucleic Acid Amplification Test) result in anal specimens four weeks after treatment initiation, among participants with a LGV-positive NAAT result at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Differentiation of reinfection from treatment failure at Week 4 | 4 weeks after treatment initiation | Genotyping (ompA gene) of C. trachomatis-positive specimens obtained at week 4 to differentiate reinfection (different ompA-genotype, or unprotected anal intercourse with an untreated/new partner) from treatment failure (identical ompA-genotype, or no anal intercourse/consistent condom use since inclusion). |
| Chlamydia trachomatis bacterial load in anal specimens | Baseline and 4 weeks after treatment initiation | C. trachomatis load will be measured at baseline and four weeks after treatment initiation using quantitative real-time PCR, reported as the number of DNA copies per microliter. |
| Molecular mechanisms of doxycycline resistance | Baseline and 4 weeks after treatment initiation | Identification of molecular mechanisms for doxycycline resistance by amplification and sequencing of target genes (including 16S rRNA gene) in all LGV-positive specimens collected at baseline and four weeks after treatment initiation. |
| Adherence to doxycycline treatment | From treatment initiation to 4 weeks after treatment initiation | Adherence to the 7-day doxycycline regimen will be evaluated using a patient self-completed daily diary, along with pill count and return of treatment packaging at the inclusion and follow-up visits. |
| Incidence of adverse events and serious adverse events | up to 6 weeks | Number and percentage of participants experiencing adverse events (AEs) and serious adverse events (SAEs) related or unrelated to doxycycline, recorded in the e-CRF |
Countries
France
Contacts
CONTACTCharles CAZANAVE, Pr
CONTACTOlivia PEUCHANT, PharmD
Outcome results
None listed