Evaluation of Doxycycline Post-exposure Prophylaxis to Reduce Sexually Transmitted Infections in PrEP Users and HIV-infected Men Who Have Sex With Men

Sponsor

University of California, San Francisco (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03980223

Collaborator

University of Washington (Other), National Institute of Allergy and Infectious Diseases (NIAID) (NIH), Mayne Pharma International Pty Ltd (Industry), San Francisco Department of Public Health (Other)

637

Enrollment

Locations

Arms

41.5

Anticipated Duration (Months)

212.3

Patients Per Site

5.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to understand if taking an antibiotic called doxycycline by mouth as soon as possible after sexual contact without a condom can reduce the risk of sexually transmitted infections (STIs), including gonorrhea, chlamydia and syphilis. The study will also look at the safety of doxycycline PEP and the impact that PEP may have on the bacteria that cause STIs as well as on bacteria that normally live on the body. While doxycycline is approved by the Food and Drug Administration (FDA), taking doxycycline immediately after sexual contact to prevent infection is investigational and is not approved by the FDA for this use. Participants will take part in the study for 1 year.

Condition or Disease	Intervention/Treatment	Phase
Gonorrhea Chlamydia Syphilis	Drug: Doxycycline Hyclate Delayed-Release 200 mg	Phase 4

Detailed Description

The overarching goal is to assess the effectiveness of doxycycline PEP on incidence of STIs and tetracycline resistance among STIs and commensal bacteria to inform public health policy. Participants will be randomized 2:1, with a greater number receiving doxycycline PEP compared with the standard of care control, to maximize data on safety, tolerability, adherence coverage of sexual acts, and resistance data in participants randomized to doxycycline PEP, without negatively impacting power to measure effectiveness. Participants will be counseled about the preliminary effectiveness data from IPERGAY, and the potential for antimicrobial resistance (AMR) in STIs or other bacteria. Possibility of unreported doxycycline us in the control arm (contamination) will be monitored through retrospective batch testing of doxycycline metabolites in hair, to detect doxycycline use in the prior 3 months. 53

Eligible participants randomized 2:1 to receive PEP will receive open-label doxycycline 200 mg to be taken ideally within 24 hours but no later than 72 hours after condomless sexual contact (oral or anal). 200 mg of doxycycline will be taken at most once per 24 hour period regardless of the number of sexual acts occurring during this time period. Sexual activity will be recorded for both arms of the study (doxycycline PEP and control condition) by the participant using a smartphone application that will be adapted for study use; this will enable comparable assessment of risk in the two arms. PEP pill-taking will also be measured by the app to enable assessment of coverage of sex acts by PEP. Sexual activity and adherence will also be assessed in person at quarterly visits. STI testing will be conducted quarterly from three anatomic sites (pharyngeal, rectal and urinary) and blood for syphilis testing. Participants with a positive STI test will return for STI treatment and for swabs of the affected site for resistance testing; culture based for gonorrhea (GC) and molecular methods for CT and syphilis. Those with a serologic test that indicates a new syphilis infection will have swabs of any current active lesion as well as mucosal swabs from the oropharynx. Nares and oropharyngeal swabs will be obtained at baseline, 6 and 12 months to evaluate tetracycline resistance in S. aureus among carriers and in commensal Neisseria species.

Stool samples from 100 participants on the doxycycline PEP arm - 50 MSM living with HIV and 50 HIV uninfected MSM on pre-exposure prophylaxis (PrEP) - will be collected at baseline, 6 and 12 months to evaluate effects of intermittent doxycycline on the gut resistome, using 16s ribosomal RNA amplification to study tetracycline resistance genes. Rectal swabs will be collected and archived in all participants at baseline, 6, and 12 months for future studies of the impact of doxycycline PEP on the enteric microbiome and resistome.

Study population: This study will enroll 390 HIV-infected participants and 390 persons taking PrEP, for a total sample size of 780. An approximately equal number of participants in each of these cohorts (and in each study arm) will be enrolled in San Francisco and Seattle.

Current or planned initiation of PrEP use is an eligibility criterion for enrollment, because this population of MSM has high rates of STIs and are typically seen quarterly for PrEP visits. However, participants may opt to stop PrEP use at any time during the study without affecting their involvement in the study. Any HIV-uninfected participants who subsequently seroconvert will be managed clinically by the study site according to local practice (appropriate counseling, clinical evaluation and immediate linkage to clinical and psychosocial services). These participants will also be retained in the study unless they choose to discontinue study participation.

Study Design

Study Type:

Interventional

Actual Enrollment :

637 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Open-label randomized clinical trialOpen-label randomized clinical trial

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Evaluation of Doxycycline Post-exposure Prophylaxis to Reduce Sexually Transmitted Infections in PrEP Users and HIV-infected Men Who Have Sex With Men

Actual Study Start Date :

Nov 26, 2019

Anticipated Primary Completion Date :

May 13, 2023

Anticipated Study Completion Date :

May 13, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Doxy PEP Doxycycline 200mg in addition to standard of care STI testing and treatment	Drug: Doxycycline Hyclate Delayed-Release 200 mg 200 mg of doxycycline taken by mouth after condomless sexual contact as post exposure prophylaxis (PEP)
No Intervention: Control The control arm will consist of standard of care STI testing and treatment

Arm

Intervention/Treatment

Experimental: Doxy PEP

Doxycycline 200mg in addition to standard of care STI testing and treatment

Drug: Doxycycline Hyclate Delayed-Release 200 mg

200 mg of doxycycline taken by mouth after condomless sexual contact as post exposure prophylaxis (PEP)

No Intervention: Control

The control arm will consist of standard of care STI testing and treatment

Outcome Measures

Primary Outcome Measures

Incidence of GC, CT or syphilis [1 year]
Combined incidence of GC, CT, or early syphilis infection by by laboratory-based diagnosis

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Willing and able to give written informed consent
Age ≥ 18 years
Male sex at birth
Previously HIV-diagnosed OR HIV-seronegative at the time of last test within the past month and a current prescription for PrEP (both daily or event-driven permitted) or plan to start PrEP within 30 days after the enrollment visit
Condomless anal or oral sexual contact with ≥ 1 male sex-at-birth partners in the past 12 months
Diagnosed with GC, CT or early syphilis (primary, secondary or early latent) in the past 12 months. Note: self report of STI is acceptable if documentation not available. If the participant reports an incident STI in the past year at the same clinic where the participant will be enrolled, this diagnosis should be confirmed by chart review prior to enrollment. If the diagnosis from this clinic cannot be confirmed, the participant should not be enrolled. If the STI was reported at a clinical site that is not the study site, and records cannot be obtained, self-report will suffice.

Note: Syphilis diagnosis within the last year refers to primary syphilis, secondary syphilis, and documented early latent syphilis (< 1 year since last syphilis diagnosis or negative test). Known late latent syphilis or latent syphilis of unknown duration would not qualify. Positive syphilis titers which represent serofast status and not active disease do not qualify as a syphilis diagnosis. Clinician judgement regarding qualifying syphilis diagnosis should be sought when the diagnosis of syphilis in the past year is not clear or if there is a question about serofast status vs. active infection.

Exclusion Criteria:

Allergy to tetracycline class
Current medications which may impact doxycycline metabolism or that are contraindicated with doxycycline, as per the prescribing information. These include systemic retinoids, barbiturates, carbamazepine, and phenytoin.
Current use of warfarin, as intermittent doxycycling use can lead to an unpredictable impact on INR
Anticipated use of doxycycline during the coming 12 months for non-STI prevention (e.g., acne treatment).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	San Francisco City Clinic / San Francisco Department of Public Health	San Francisco	California	United States	94103
2	University of California, San Francisco / Zuckerberg San Francisco General Hospital/UCSF	San Francisco	California	United States	94110
3	University of Washington	Seattle	Washington	United States	98195