Clinical trial NCT03532464: Azithromycin Compared With Doxycycline for Treating Anorectal Chlamydia Trachomatis Infection Concomitant to a Vaginal Infection
Official title: Randomized, Open-label, Multicenter Study of Azithromycin Compared With Doxycycline for Treating Anorectal Chlamydia Trachomatis Infection Concomitant to a Vaginal Infection
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Chlamydia Trachomatis Infection
Vaginal Infection
Anal Infection
Keywords: Chlamydia Trachomatis
Infection
Vaginal
Anal
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
Collaborators: name: USC EA 3671 Infections humaines à mycoplasmes et à chlamydiae
First posted: 2018-05-22
Enrollment: 460
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, open-label, multicenter
Primary purpose: TREATMENT

Brief summary: Chlamydia trachomatis is the most commonly reported bacterial sexually transmitted infection (STI), especially among young women. Up to 75% of C. trachomatis infected women are asymptomatic. If untreated, C. trachomatis infection can cause sequelae such as pelvic inflammatory disease, ectopic pregnancy and tubal factor infertility. C. trachomatis can also cause anorectal infections, which are typically asymptomatic. Among women with urogenital chlamydial infection, around 36-91% also had concurrent anorectal chlamydial. Notably, there was no association with anal intercourse in the studies that reported it. However, guidelines do not recommend routine anorectal testing, but restricted testing in people who are in high-risk groups, report anal sexual behavior, or have anal symptoms, i.e., on selective indications. This is in contrast to urogenital testing, which is a routine procedure in STI care services.

The anal transmission of C. trachomatis in women may occur by autoinoculation from the vagina due to the close proximity of the vagina and the anus. C. trachomatis could lead to a persistent infection in the lower gastrointestinal tract, suggesting the potential role of autoinoculation of cervical chlamydial infection from the rectal site. Such (repeat) urogenital infections could lead to reproductive tract morbidity. Recommended treatments for C. trachomatis infections are a single 1g dose of azithromycin or 100mg of doxycycline 2 times a day for 7 days. Although these two regimens are equivalent for urogenital infection, no study has compared the effectiveness of these two treatments on anorectal infection. If rectal C. trachomatis is a hidden reservoir influencing transmission rates, and considering the potential complications of cervical infections, providing further evidence of the need for effective rectal treatments among women is highly relevant.

Detailed description: A possible reason for C. trachomatis detection after treatment may be transmission (self or another) or treatment failure. Whether antimicrobial treatment failure for C. trachomatis plays a role remains poorly understood. There is no evidence of antimicrobial resistance and testing for antimicrobial resistance for C. trachomatis is not routinely available. The hypothesis of transmission is most likely, especially as recontamination is very common among young people, either due to an untreated partner or a new partner. When these two conditions are ruled out, the hypothesis of autoinoculation from rectum to vagina is quite probable.

With regard to anorectal C. trachomatis infections, some studies concluded that azithromycin is a suboptimal treatment\], while another study found doxycycline and azithromycin treatment to be equally effective. However, there are no robust studies that shows conclusive evidence relating to a suboptimal effect of any time of treatment or that prefers one treatment over the other.

The current study attempts to clarify the above question. The team propose to conduct the first open-label randomized controlled trial comparing the efficacy (measured as microbial cure) of a single 1g dose of azithromycin versus 100 mg of doxycycline twice daily for seven days for the treatment of anorectal C. trachomatis infection concurrent to urogenital infection in women. The experimental group will include women with C. trachomatis-positive vaginal and anorectal swabs treated with doxycycline twice daily for seven days with one tablet of 100 mg of doxycycline in the morning and evening. The control group will include women with C. trachomatis-positive vaginal and anorectal swabs treated with azithromycin consisting of four tablets of 250 mg of azithromycin in one intake.

The team made the hypothesis that the efficacy of azithromycin for anorectal infections may be lower than that of doxycycline, resulting in reinfections by autoinoculation from rectum to vagina. The expected result is that the number of women with a C. trachomatis-positive NAAT result in the anorectal swab will be significantly higher in the control group than in the experimental group after treatment.

Eligibility criteria: Inclusion Criteria:

* Female
* Age \> 18 years
* Negative β-hCG urinary assay and efficacious contraception for participant consulting in specialist centre
* Participant requesting an abortion at a pregnancy termination centre and efficacious contraception after abortion
* C. trachomatis-positive test for vaginal specimen using a Nucleic Acid Amplification Test (NAAT)
* Sexually active
* Consultation in one of the participating centers
* Agree to be contacted for follow-up
* Member or beneficiary of a social security system
* Free written informed consent signed by the participant and the investigator (no later than the inclusion day and before performing any examination required for the study)

Exclusion Criteria:

* Women who have symptoms suggesting pelvic inflammatory disease (PID)
* Receipt of an antibiotic with antichlamydial activity within 21 days before screening or between screening and enrollment
* Contraindications to tetracyclines, macrolides or ketolids (including allergy and treatment with colchicine, cisapride, ergot alkaloids and retinoids)
* Inability to swallow pills
* Refusal to participate in the study
* Objectives of the study not understood.
* Breast-feeding
* Patients with serious cardiac diseases: documented prolongation of the QT tract of the ECG, cardiac arrhythmias, advanced heart failure (classification New York Heart Association or NYHA \>III)
* Patients treated with anticoagulants or drug with a definite potential of "Torsades de Pointe" or prolongation of the QT tract of the electrocardiogram
* Patients with severe liver diseases

Primary outcomes:
measure: Nucleic Acid Amplification Assay result
timeFrame: 6 weeks
Secondary outcomes:
measure: the number of women with an anorectal C. trachomatis infection concomitant to a vaginal infection
timeFrame: Day 1
measure: C. trachomatis genotype
timeFrame: Day 1
measure: C. trachomatis genotype
timeFrame: 6 weeks
measure: C. trachomatis genotype
timeFrame: 4 months
Other outcomes:
Locations:
city: Marseille
country: France
facility: CeGIDD - Marseille
state: Marignane
city: Bordeaux
country: France
facility: CeGGID - Bordeaux
city: Bordeaux
country: France
facility: CHU de Bordeaux
city: Nantes
country: France
facility: CHU de Nantes
city: Paris
country: France
facility: Hôpital Hôtel Dieu
city: Roubaix
country: France
facility: Hôpital de Roubaix
city: Tours
country: France
facility: CHRU Tours
Study officials:
affiliation: University Hospital, Bordeaux
name: Bertille de Barbeyrac, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rank RG, Yeruva L. Hidden in plain sight: chlamydial gastrointestinal infection and its relevance to persistence in human genital infection. Infect Immun. 2014 Apr;82(4):1362-71. doi: 10.1128/IAI.01244-13. Epub 2014 Jan 13.
citation: Kong FY, Tabrizi SN, Fairley CK, Vodstrcil LA, Huston WM, Chen M, Bradshaw C, Hocking JS. The efficacy of azithromycin and doxycycline for the treatment of rectal chlamydia infection: a systematic review and meta-analysis. J Antimicrob Chemother. 2015 May;70(5):1290-7. doi: 10.1093/jac/dku574. Epub 2015 Jan 29.
citation: Kong FY, Hocking JS. Treatment challenges for urogenital and anorectal Chlamydia trachomatis. BMC Infect Dis. 2015 Jul 29;15:293. doi: 10.1186/s12879-015-1030-9.
citation: Peuchant O, Lhomme E, Martinet P, Grob A, Baita D, Bernier C, Gibaud SA, Le Hen I, Le Naour E, Trignol-Viguier N, Lanotte P, Lefebvre P, Vachee A, Girard T, Loubinoux J, Bebear C, Ghezzoul B, Roussillon C, Kret M, de Barbeyrac B; CHLAZIDOXY Study Group. Doxycycline versus azithromycin for the treatment of anorectal Chlamydia trachomatis infection in women concurrent with vaginal infection (CHLAZIDOXY study): a multicentre, open-label, randomised, controlled, superiority trial. Lancet Infect Dis. 2022 Aug;22(8):1221-1230. doi: 10.1016/S1473-3099(22)00148-7. Epub 2022 May 9.
citation: Peuchant O, Lhomme E, Kret M, Ghezzoul B, Roussillon C, Bebear C, Perry F, de Barbeyrac B; and the Chlazidoxy study group. Randomized, open-label, multicenter study of azithromycin compared with doxycycline for treating anorectal Chlamydia trachomatis infection concomitant to a vaginal infection (CHLAZIDOXY study). Medicine (Baltimore). 2019 Feb;98(7):e14572. doi: 10.1097/MD.0000000000014572.