Azithromycin Compared With Doxycycline for Treating Anorectal Chlamydia Trachomatis Infection Concomitant to a Vaginal Infection (CHLAZIDOXY)

Randomized, Open-label, Multicenter Study of Azithromycin Compared With Doxycycline for Treating Anorectal Chlamydia Trachomatis Infection Concomitant to a Vaginal Infection

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.

Study Overview

• Status: Unknown
• Conditions: Chlamydia Trachomatis Infection; Vaginal Infection; Anal Infection
• Intervention / Treatment: Drug: doxycycline; Drug: azithromycin

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.

• Study Type: Interventional
• Enrollment (Anticipated): 460
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Bertille de Barbeyrac, MD; Phone Number: + 33 5 57 57 16 25; Email: bertille.de-barbeyrac@u-bordeaux.fr
• Study Contact Backup: Name: Olivia Peuchant, MD; Phone Number: + 33 5 57 57 16 25; Email: olivia.peuchant@u-bordeaux.fr

Study Locations

• France
  • Bordeaux, France, 33000
    • CHU de Bordeaux
    • Contact: Nathalie RAE, MD; Phone Number: +33556795888; Email: nathalie.rae@chu-bordeaux.fr
  • Bordeaux, France, 33000
    • CeGGID - Bordeaux
    • Contact: Isabelle Le Hen, MD; Phone Number: +33557224660; Email: i.lehen@gironde.fr
  • Nantes, France, 44000
    • CHU de Nantes
    • Contact: Claire Bernier, MD; Phone Number: +3320087009; Email: claire.bernier@chu-nantes.fr
  • Paris, France, 75004
    • Hôpital Hotel Dieu
    • Contact: Thomas Girard, MD; Phone Number: +33142348724; Email: thomas.girard@aphp.fr
  • Roubaix, France, 59170
    • Hôpital de Roubaix
    • Contact: Philippe Lefebvre, MD, PhD; Phone Number: +33320993230; Email: philippe.lefbvre@ch-roubaix.fr
  • Tours, France, 37000
    • CHRU Tours
    • Contact: Nathalie Trignol-Viguier, MD; Phone Number: +33247474743; Email: n.trignol@chu-tours.fr
  • Marignane
    • Marseille, Marignane, France, 13700
      • CeGIDD - Marseille
      • Contact: Pervenche Martinet, MD; Phone Number: +33413317800; Email: pervenche.martinet@departement13.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patient treated by doxycycline; The patients in the doxycycline group take one tablet of 100 mg twice a day for seven days. Antibiotics will be dispensed in their usual packaging with a clinical trial label.	Drug: doxycycline; The patients in the doxycycline group take one tablet of 100 mg twice a day for seven days.; Other Names: Treatment
Active Comparator: Patients treated by azithromycin; The patients in the azithromycin group take 4 tablets of 250 mg in the morning as a single dose. Antibiotics will be dispensed in their usual packaging with a clinical trial label.	Drug: azithromycin; The route of administration is oral. It is administered at a dose of 1 g (4 tablets), as a single dose with or without food.; Other Names: Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nucleic Acid Amplification Assay result	C. trachomatis-positive NAAT result in anorectal specimens after treatment	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the number of women with an anorectal C. trachomatis infection concomitant to a vaginal infection	The prevalence of anorectal C. trachomatis infection concomitant to a vaginal infection is the number of women with an anorectal C. trachomatis infection divided by the total number of women included in the study	Day 1
C. trachomatis genotype	The number of subjects for whom the same C. trachomatis genotype profile will be identified in the vaginal-positive and anorectal-positive specimens obtained on the day of inclusion (self-infection), and in the anorectal-positive specimen obtained six weeks after treatment initiation (persistence) and in the vaginal-positive specimen obtained four months after treatment (autoinoculation).	Day 1
C. trachomatis genotype	The number of subjects for whom the same C. trachomatis genotype profile will be identified in the vaginal-positive and anorectal-positive specimens obtained on the day of inclusion (self-infection), and in the anorectal-positive specimen obtained six weeks after treatment initiation (persistence) and in the vaginal-positive specimen obtained four months after treatment (autoinoculation).	6 weeks
C. trachomatis genotype	The number of subjects for whom the same C. trachomatis genotype profile will be identified in the vaginal-positive and anorectal-positive specimens obtained on the day of inclusion (self-infection), and in the anorectal-positive specimen obtained six weeks after treatment initiation (persistence) and in the vaginal-positive specimen obtained four months after treatment (autoinoculation).	4 months

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Collaborators: USC EA 3671 Infections humaines à mycoplasmes et à chlamydiae
• Investigators: Principal Investigator: Bertille de Barbeyrac, MD, University Hospital, Bordeaux

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2018
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: May 9, 2018
• First Submitted That Met QC Criteria: May 9, 2018
• First Posted (Actual): May 22, 2018

Study Record Updates

• Last Update Posted (Actual): June 4, 2018
• Last Update Submitted That Met QC Criteria: May 31, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Infection; Vaginal; Anal; Chlamydia Trachomatis
• Additional Relevant MeSH Terms: Pathologic Processes; Sexually Transmitted Diseases; Disease Attributes; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Chlamydiaceae Infections; Sexually Transmitted Diseases, Bacterial; Infections; Communicable Diseases; Chlamydia Infections; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Doxycycline; Azithromycin
• Other Study ID Numbers: CHUBX 2016/26

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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