Trial of Azithromycin vs. Doxycycline for the Treatment of Rectal Chlamydia in MSM

A Phase 4, Randomized, Double-Blinded, Placebo-Controlled Trial of Azithromycin Versus Doxycycline for the Treatment of Rectal Chlamydia in Men Who Have Sex With Men

A clinical trial to compare the efficacy of azithromycin (Arm 1) vs. doxycycline (Arm 2) administered per CDC's STD Treatment Guidelines for rectal Chlamydia trachomatis (CT) in men who have sex with men (MSM). Subjects will be males aged = / > 18 years with a microbiologically confirmed diagnosis of rectal CT and at least one male sex partner in the past 12 months. The trial will be conducted at two sites in the US and will enroll up to 274 total subjects to achieve 246 subjects who contribute to the primary analysis. The duration of this study will be approximately 16 months 22 months with subject participation duration 29 days. The primary objective of this study is to compare the efficacy of azithromycin vs. doxycycline for treatment of rectal CT infection in MSM based on microbiologic cure (negative NAAT) at Day 29.

Study Overview

• Status: Completed
• Conditions: Anal Chlamydia Infection
• Intervention / Treatment: Drug: Azithromycin; Other: Placebo; Drug: Doxycycline

Detailed Description

A Phase 4, multi-center, randomized, double-blinded, placebo-controlled trial to compare the efficacy of azithromycin (Arm 1) vs. doxycycline (Arm 2) administered per CDC's STD Treatment Guidelines for rectal Chlamydia trachomatis (CT) in men who have sex with men (MSM). The effect of Lymphogranuloma Venereum (LGV) infection on microbiologic cure in MSM with rectal CT will also be assessed. Arm 1 will comprise of subjects receiving 1 gram of Azithromycin (4 capsules of 250 mg) orally as a single dose, and Doxycycline placebo (1 capsule) orally twice daily for 7 days. Arm 2 will comprise of subjects receiving 100 mg of Doxycycline (1 capsule) administered orally twice daily for 7 days, and Azithromycin placebo (4 capsules) administered orally as a single dose. Subjects will be males aged = / >18 years with a microbiologically confirmed diagnosis of rectal CT and at least one male sex partner in the past 12 months. The trial will be conducted at two sites in the US and will enroll up to 274 total subjects to achieve 246 subjects who contribute to the primary analysis. The duration of this study will be approximately 22 months with subject participation duration 29 days. The primary objective of this study is to compare the efficacy of azithromycin vs. doxycycline for treatment of rectal CT infection in MSM based on microbiologic cure (negative NAAT) at Day 29. The secondary objectives are: 1) to assess the effect of LGV infection on microbiologic cure in MSM with rectal CT at Days 15 and 29 and 2) to compare the efficacy of azithromycin vs. doxycycline for treatment of rectal CT in MSM based on microbiologic cure at Day 15.

• Study Type: Interventional
• Enrollment (Actual): 177
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Fenway Health - The Fenway Institute
  • Washington
    • Seattle, Washington, United States, 98104-2499
      • University of Washington - Harborview Medical Center - Center for AIDS and STD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 97 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Willing and able to understand and provide written informed consent before initiation of any study procedures.
2. Willing and able to comply with planned study procedures for all study visits.
3. Male sex at birth and aged = / > 18 years with valid contact information.
4. At least one male sex partner (oral or anal) in the past 12 months.
5. Untreated rectal CT diagnosed by a positive NAAT result.
6. Willingness to abstain from condomless receptive anal sex during the trial.
7. Willingness to complete a 7-day study drug regimen.

Exclusion Criteria:

1. Current clinical diagnosis of acute proctitis per the CDC's 2015 STD Treatment Guidelines: symptoms of anorectal pain, tenesmus, and/or rectal discharge with anoscopy findings confirming inflammation.
2. Concomitant untreated gonorrhea (rectal, pharyngeal, or urethral) or known exposure to gonorrhea in the time between CT testing and study enrollment.
3. Clinical diagnosis of concomitant untreated primary or secondary syphilis.
4. Known allergy to tetracyclines or macrolides.

5. Received antimicrobial therapy active against C. trachomatis within 21 days of positive rectal CT NAAT result, or between the positive CT NAAT result and study enrollment*.

   *This includes subjects treated empirically on the day of testing due to known exposure to gonorrhea or chlamydia, as well as enrollment in another study using antimicrobial therapy active against C. trachomatis, or planned enrollment in such a study during their time in this trial. Specifically, use of the following antibiotics is an exclusion criterion: azithromycin and other macrolides, doxycycline and related tetra- or glycylcyclines, fluoroquinolones, rifampin, quinupristin-dalfopristin, and linezolid.

6. Plans to move to another location that would preclude study follow-up appointments in clinic or by mail-in in the next 30 days.
7. Use of any investigational drug contraindicated to treatment with azithromycin or doxycycline within 7 days before enrollment.
8. Previous enrollment in this trial.
9. Any other condition that, in the opinion of the investigator, would interfere with participation in the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; 1 gram of Azithromycin (4 capsules of 250 mg) administered orally as a single dose on Day 1, and Doxycycline placebo (1 capsule) administered orally twice daily for 7 days starting on Day 1. N=123	Drug: Azithromycin; Azithromycin monohydrate is a macrolide antibacterial drug, FDA-approved in the US for the treatment of Chlamydia trachomatis (CT) in dose 1 gram (4 capsules of 250 mg), administered orally as a single dose.; Other: Placebo; Azithromycin placebo (4 capsules), administered orally as a single dose; Doxycycline placebo (1 capsule), administered orally twice daily for 7 days.
Experimental: Arm 2; 100 mg of Doxycycline (1 capsule) administered orally twice daily for 7 days starting on Day 1, and Azithromycin placebo (4 capsules) administered orally as a single dose on Day 1. N=123	Other: Placebo; Azithromycin placebo (4 capsules), administered orally as a single dose; Doxycycline placebo (1 capsule), administered orally twice daily for 7 days.; Drug: Doxycycline; Doxycycline hyclate is an antibacterial drug synthetically derived from oxytetracycline, FDA-approved in the US for the treatment of Chlamydia trachomatis (CT) as a course of 100 mg (1 capsule), administered orally twice daily for 7 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Proportion of Subjects With Microbiologic Cure (Negative Rectal CT NAAT Result) at Day 29	Microbiologic cure was based on rectal CT (Chlamydia trachomatis) NAAT (nucleic acid amplification test) result. The proportion of subjects with microbiologic cure in each study arm at Day 29 is reported in this outcome measure.	Day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Proportion of Subjects With Microbiologic Cure (Negative Rectal CT NAAT Result) at Day 15	Microbiologic cure was based on rectal CT (Chlamydia trachomatis) NAAT (nucleic acid amplification test) result. The proportion of subjects with microbiologic cure in each study arm at Day 15 is reported in this outcome measure.	Day 15
The Proportion of Subjects With Microbiologic Cure (Negative Rectal CT NAAT Result) Within the Subgroup of Non-LGV (Lymphogranuloma Venereum) Infected at Baseline	Microbiologic cure was based on rectal CT (Chlamydia trachomatis) NAAT (nucleic acid amplification test) result. The proportion of subjects with microbiologic cure in each study arm at Day 15 is reported in this outcome measure. LGV strains of CT were identified via multiplex PCR (Polymerase Chain Reaction) on positive CT NAAT specimens.	Day 15
The Proportion of Subjects With Microbiologic Cure (Negative Rectal CT NAAT Result) Within the Subgroup of Non-LGV (Lymphogranuloma Venereum) Infected at Baseline	Microbiologic cure was based on rectal CT (Chlamydia trachomatis) NAAT (nucleic acid amplification test) result. The proportion of subjects with microbiologic cure in each study arm at Day 29 is reported in this outcome measure. LGV strains of CT were identified via multiplex PCR (Polymerase Chain Reaction) on positive CT NAAT specimens.	Day 29
The Proportion of Subjects With Microbiologic Cure (Negative Rectal CT NAAT Result) Within the Subgroup of LGV (Lymphogranuloma Venereum) Infected at Baseline	Microbiologic cure was based on rectal CT (Chlamydia trachomatis) NAAT (nucleic acid amplification test) result. The proportion of subjects with microbiologic cure in each study arm at Day 15 is reported in this outcome measure. LGV strains of CT were identified via multiplex PCR (Polymerase Chain Reaction) on positive CT NAAT specimens.	Day 15
The Proportion of Subjects With Microbiologic Cure (Negative Rectal CT NAAT Result) Within the Subgroup of LGV (Lymphogranuloma Venereum) Infected at Baseline	Microbiologic cure was based on rectal CT (Chlamydia trachomatis) NAAT (nucleic acid amplification test) result. The proportion of subjects with microbiologic cure in each study arm at Day 29 is reported in this outcome measure. LGV strains of CT were identified via multiplex PCR (Polymerase Chain Reaction) on positive CT NAAT specimens.	Day 29

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Publications and helpful links

General Publications

• Dombrowski JC, Wierzbicki MR, Newman LM, Powell JA, Miller A, Dithmer D, Soge OO, Mayer KH. Doxycycline Versus Azithromycin for the Treatment of Rectal Chlamydia in Men Who Have Sex With Men: A Randomized Controlled Trial. Clin Infect Dis. 2021 Sep 7;73(5):824-831. doi: 10.1093/cid/ciab153.

Study record dates

Study Major Dates

• Study Start (Actual): July 13, 2018
• Primary Completion (Actual): February 21, 2020
• Study Completion (Actual): February 21, 2020

Study Registration Dates

• First Submitted: June 28, 2018
• First Submitted That Met QC Criteria: July 30, 2018
• First Posted (Actual): August 1, 2018

Study Record Updates

• Last Update Posted (Actual): January 7, 2021
• Last Update Submitted That Met QC Criteria: December 10, 2020
• Last Verified: January 25, 2019

More Information

Terms related to this study

• Keywords: Efficacy; Azithromycin; MSM; Doxycycline; Phase 4; Rectal Chlamydia
• Additional Relevant MeSH Terms: Infections; Communicable Diseases; Sexually Transmitted Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Chlamydiaceae Infections; Sexually Transmitted Diseases, Bacterial; Chlamydia Infections; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Doxycycline; Azithromycin
• Other Study ID Numbers: 17-0092

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No