Anal Chlamydia Infection
Conditions
Keywords
Azithromycin, Doxycycline, Efficacy, MSM, Phase 4, Rectal Chlamydia
Brief summary
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.
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.
Interventions
DRUGAzithromycin
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.
DRUGDoxycycline
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.
OTHERPlacebo
Azithromycin placebo (4 capsules), administered orally as a single dose; Doxycycline placebo (1 capsule), administered orally twice daily for 7 days.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 99 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Subjects With Microbiologic Cure (Negative Rectal CT NAAT Result) at Day 29 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Subjects With Microbiologic Cure (Negative Rectal CT NAAT Result) at Day 15 | 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. |
| The Proportion of Subjects With Microbiologic Cure (Negative Rectal CT NAAT Result) Within the Subgroup of Non-LGV (Lymphogranuloma Venereum) Infected at Baseline | 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. LGV strains of CT were identified via multiplex PCR (Polymerase Chain Reaction) on positive CT NAAT specimens. |
| The Proportion of Subjects With Microbiologic Cure (Negative Rectal CT NAAT Result) Within the Subgroup of LGV (Lymphogranuloma Venereum) Infected at Baseline | 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. LGV strains of CT were identified via multiplex PCR (Polymerase Chain Reaction) on positive CT NAAT specimens. |
Countries
United States
Participant flow
Recruitment details
Participants recruited for the study were men who have sex with men diagnosed with rectal chlamydia based on a positive rectal Chlamydia trachomatis (CT) nucleic acid amplification test (NAAT) result. The first participant was enrolled on 13 July 2018, and the last participant was enrolled in January 2020.
Participants by arm
| Arm | Count |
|---|---|
| Azithromycin + Doxycycline Placebo 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=89
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.
Placebo: Doxycycline placebo (1 capsule), administered orally twice daily for 7 days. | 89 |
| Doxycycline + Azithromycin Placebo 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=88
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.
Placebo: Azithromycin placebo (4 capsules), administered orally as a single dose. | 88 |
| Total | 177 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Health related event | 0 | 1 |
| Overall Study | Lost to Follow-up | 5 | 5 |
| Overall Study | Not eligible at enrollment | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Azithromycin + Doxycycline Placebo | Doxycycline + Azithromycin Placebo | Total |
|---|---|---|---|
| Age, Continuous | 33.6 years STANDARD_DEVIATION 10.8 | 33.9 years STANDARD_DEVIATION 11.6 | 33.7 years STANDARD_DEVIATION 11.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants | 21 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 71 Participants | 67 Participants | 138 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants |
| Inguinal Lymphadenopathy No | 86 Participants | 83 Participants | 169 Participants |
| Inguinal Lymphadenopathy Not Available | 0 Participants | 1 Participants | 1 Participants |
| Inguinal Lymphadenopathy Yes | 3 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 10 Participants | 12 Participants | 22 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 5 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 16 Participants | 6 Participants | 22 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 5 Participants | 8 Participants |
| Race (NIH/OMB) White | 54 Participants | 58 Participants | 112 Participants |
| Rectal CT Symptomatic Status Asymptomatic | 71 Participants | 74 Participants | 145 Participants |
| Rectal CT Symptomatic Status Not Available | 0 Participants | 1 Participants | 1 Participants |
| Rectal CT Symptomatic Status Symptomatic | 18 Participants | 13 Participants | 31 Participants |
| Region of Enrollment United States | 89 participants | 88 participants | 177 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 89 Participants | 88 Participants | 177 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 89 | 0 / 87 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 89 | 1 / 87 |
Outcome results
Primary
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.
Time frame: Day 29
Population: The Complete Case population included randomized subjects who met all inclusion/exclusion criteria at enrollment, had a positive baseline rectal CT NAAT result, and had a Day 29 microbiologic result available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Azithromycin + Doxycycline Placebo | The Proportion of Subjects With Microbiologic Cure (Negative Rectal CT NAAT Result) at Day 29 | 0.74 proportion of participants |
| Doxycycline + Azithromycin Placebo | The Proportion of Subjects With Microbiologic Cure (Negative Rectal CT NAAT Result) at Day 29 | 1.00 proportion of participants |
p-value: <0.00195% CI: [0.16, 0.36]Chi-squared
Secondary
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.
Time frame: Day 15
Population: The Complete Case population included randomized subjects who met all inclusion/exclusion criteria at enrollment, had a positive baseline rectal CT NAAT result, and had a Day 15 microbiologic result available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Azithromycin + Doxycycline Placebo | The Proportion of Subjects With Microbiologic Cure (Negative Rectal CT NAAT Result) at Day 15 | 0.84 proportion of participants |
| Doxycycline + Azithromycin Placebo | The Proportion of Subjects With Microbiologic Cure (Negative Rectal CT NAAT Result) at Day 15 | 0.94 proportion of participants |
95% CI: [0, 0.22]
Secondary
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.
Time frame: Day 15
Population: The Complete Case population included randomized subjects who met all inclusion/exclusion criteria at enrollment, had a positive baseline rectal CT NAAT result, had a baseline LGV infection status result, and had a post-baseline microbiologic result available. Furthermore, participants in this subgroup analyses were LGV infected at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Azithromycin + Doxycycline Placebo | The Proportion of Subjects With Microbiologic Cure (Negative Rectal CT NAAT Result) Within the Subgroup of LGV (Lymphogranuloma Venereum) Infected at Baseline | 0.75 proportion of participants |
| Doxycycline + Azithromycin Placebo | The Proportion of Subjects With Microbiologic Cure (Negative Rectal CT NAAT Result) Within the Subgroup of LGV (Lymphogranuloma Venereum) Infected at Baseline | 1.00 proportion of participants |
95% CI: [-0.28, 0.7]
Secondary
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.
Time frame: Day 29
Population: The Complete Case population included randomized subjects who met all inclusion/exclusion criteria at enrollment, had a positive baseline rectal CT NAAT result, had a baseline LGV infection status result, and had a post-baseline microbiologic result available. Furthermore, participants in this subgroup analyses were LGV infected at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Azithromycin + Doxycycline Placebo | The Proportion of Subjects With Microbiologic Cure (Negative Rectal CT NAAT Result) Within the Subgroup of LGV (Lymphogranuloma Venereum) Infected at Baseline | 0.75 proportion of participants |
| Doxycycline + Azithromycin Placebo | The Proportion of Subjects With Microbiologic Cure (Negative Rectal CT NAAT Result) Within the Subgroup of LGV (Lymphogranuloma Venereum) Infected at Baseline | 1.00 proportion of participants |
95% CI: [-0.28, 0.7]
Secondary
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.
Time frame: Day 15
Population: The Complete Case population included randomized subjects who met all inclusion/exclusion criteria at enrollment, had a positive baseline rectal CT NAAT result, had a baseline LGV infection status result, and had a post-baseline microbiologic result available. Furthermore, participants in this subgroup analyses were non-LGV infected at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Azithromycin + Doxycycline Placebo | The Proportion of Subjects With Microbiologic Cure (Negative Rectal CT NAAT Result) Within the Subgroup of Non-LGV (Lymphogranuloma Venereum) Infected at Baseline | 0.84 proportion of participants |
| Doxycycline + Azithromycin Placebo | The Proportion of Subjects With Microbiologic Cure (Negative Rectal CT NAAT Result) Within the Subgroup of Non-LGV (Lymphogranuloma Venereum) Infected at Baseline | 0.94 proportion of participants |
95% CI: [-0.01, 0.21]
Secondary
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.
Time frame: Day 29
Population: The Complete Case population included randomized subjects who met all inclusion/exclusion criteria at enrollment, had a positive baseline rectal CT NAAT result, had a baseline LGV infection status result, and had a post-baseline microbiologic result available. Furthermore, participants in this subgroup analyses were non-LGV infected at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Azithromycin + Doxycycline Placebo | The Proportion of Subjects With Microbiologic Cure (Negative Rectal CT NAAT Result) Within the Subgroup of Non-LGV (Lymphogranuloma Venereum) Infected at Baseline | 0.74 proportion of participants |
| Doxycycline + Azithromycin Placebo | The Proportion of Subjects With Microbiologic Cure (Negative Rectal CT NAAT Result) Within the Subgroup of Non-LGV (Lymphogranuloma Venereum) Infected at Baseline | 1.00 proportion of participants |
95% CI: [0.15, 0.38]