Doxycycline Versus Azithromycin for the Treatment of Rectal Chlamydia in Men Who Have Sex With Men: A Randomized Controlled Trial

BACKGROUND: Azithromycin and doxycycline are both recommended treatments for rectal Chlamydia trachomatis (CT) infection, but observational studies suggest that doxycycline may be more effective. METHODS: This randomized, double-blind, placebo-controlled trial compared azithromycin (single 1-g dose) versus doxycycline (100 mg twice daily for 7 days) for the treatment of rectal CT in men who have sex with men (MSM) in Seattle and Boston. Participants were enrolled after a diagnosis of rectal CT in clinical care and underwent repeated collection of rectal swabs for nucleic acid amplification testing (NAAT) at study enrollment and 2 weeks and 4 weeks postenrollment. The primary outcome was microbiologic cure (CT-negative NAAT) at 4 weeks. The complete case (CC) population included participants with a CT-positive NAAT at enrollment and a follow-up NAAT result; the intention-to-treat (ITT) population included all randomized participants. RESULTS: Among 177 participants enrolled, 135 (76%) met CC population criteria for the 4-week follow-up visit. Thirty-three participants (19%) were excluded because the CT NAAT repeated at enrollment was negative. Microbiologic cure was higher with doxycycline than azithromycin in both the CC population (100% 70 of 70 vs 74% 48 of 65; absolute difference, 26%; 95% confidence interval CI, 16-36%; P < .001) and the ITT population (91% 80 of 88 vs 71% 63 of 89; absolute difference, 20%; 95% CI, 9-31%; P < .001). CONCLUSIONS: A 1-week course of doxycycline was significantly more effective than a single dose of azithromycin for the treatment of rectal CT in MSM. CLINICAL TRIALS REGISTRATION: NCT03608774.