Clinical trial NCT06468462: Periodic Presumptive Treatment vs. doxyPEP for STI Control in Kenyan MSM
Official title: WHO-recommended Periodic Presumptive Treatment Versus Doxycycline Post-Exposure Prophylaxis for STI Control Among Cisgender Men Who Have Sex With Men in Kenya
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Gonorrhea Male
Chlamydia (Male)
Syphilis Male
Keywords: gonorrhea
chlamydia
syphilis
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: Aurum Institute
name: Nyanza Reproductive Health Society
name: Partners for Health and Development in Africa
name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2024-06-21
Enrollment: 2900
Sex: MALE
Minimum age (years): 18
Maximum age (years): 29
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The proposed study is an open-label randomized controlled trial with a hybrid type 1 implementation-effectiveness component comparing each intervention (i.e., STI PPT, doxyPEP) to a common control in a 2:2:1 ratio.

Approach for objective 1: We will conduct an open-label randomized clinical trial with 2900 participants to evaluate these two interventions versus the standard of care assigned in a 2:2:1 ratio, with 18 months of follow-up and rigorous culture-based and molecular analysis of AMR in NG at three MSM-friendly research clinics in Kenya.

Approach for objective 2: We will use multidisciplinary science to measure the acceptability, feasibility, and safety of these two interventions, using a conceptual model based on Proctor's Implementation Science Framework.

Approach for objective 3: Aim 1 and 2 results will inform parameters to update a stochastic model of STI transmission and cost-effectiveness analysis to project the impact of scaled-up STI PPT and doxyPEP in Kenya.
Primary purpose: OTHER

Brief summary: Men who have sex with men (MSM) are at high risk for gonorrhea and chlamydia in Kenya, where nucleic acid amplification testing is not feasible and most infections therefore go undiagnosed. We propose an open-label randomized clinical trial with 2900 participants assigned to WHO-recommended periodic presumptive treatment (PPT) or doxycycline post-exposure prophylaxis (doxyPEP), compared to standard syndromic treatment, with 18 months of follow-up and rigorous culture-based and molecular analysis of antimicrobial resistance in Neisseria gonorrhoeae. This work will provide critical data needed to inform guidelines and improve STI control among MSM in sub-Saharan Africa and other resource-limited settings, including modelled estimates of the health and economic impact of scaling up these two interventions on STI control among MSM and their partners in Kenya.

Detailed description: Men who have sex with men (MSM) are at high risk for gonorrhoea and chlamydia in Kenya, where nucleic acid amplification testing (NAAT) is not feasible, and most infections therefore go undiagnosed. In 2011, the WHO recommended periodic presumptive treatment (PPT) of Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) infections for MSM at high risk for HIV acquisition due to condomless anal intercourse with multiple sex partners or a recent STI exposure. More recently, trials in well-resourced settings have demonstrated the efficacy of doxycycline post-exposure prophylaxis (doxyPEP) for reducing NG, CT, and syphilis infections among high-risk MSM. The goal of this study is to evaluate the impact and cost-effectiveness of WHO-recommended PPT versus doxyPEP compared to standard syndromic treatment among Kenyan MSM. This study aims to (1) evaluate the effectiveness and impact on antimicrobial resistance in NG of WHO-recommended PPT given every 3 months and of doxy-PEP taken 24-72 hours after condomless sex for reducing STI burden among Kenyan MSM; (2) assess the acceptability, feasibility, and safety of implementing WHO-recommended PPT and doxy-PEP compared to standard care among providers and patients; and (3) model the health and economic impact of scaling up WHO-recommended STI PPT and doxyPEP compared to standard of care on STI control among MSM and their partners in Kenya. We will conduct an open-label randomized trial with 2900 participants to evaluate these two interventions versus standard care assigned in a 2:2:1 ratio, with 18 months of follow-up at three MSM-friendly research clinics in Kenya. Results will inform parameters to update a stochastic model of STI transmission and cost-effectiveness analysis to project the impact of scaled-up STI PPT and doxyPEP in Kenya. This work will provide the critical data needed to inform guidelines and improve STI control among this key population in sub-Saharan Africa and other resource-limited settings.

Eligibility criteria: Inclusion Criteria:

* 18-29 years old
* Assigned male sex at birth
* Identifies as male (cis-gender)
* Reports condomless anal intercourse with a man in the past 6 months
* Reports multiple male sex partners OR a male sex partner with a syndromic (urethritis, proctitis, or genital ulcer disease) or laboratory-diagnosed sexually transmitted infection in the past 6 months
* Willing and able to provide written informed consent and participate in all study procedures
* Planning to remain in the study area for 18 months

Exclusion Criteria:

* Unable to understand the study purpose and procedures
* Allergy to cephalosporin (cefixime), macrolide (erythromycin or azithromycin), or tetracycline (doxycycline) class antibiotics
* Recent use of prolonged antibiotics (≥14-day course in the month before enrolment)
* Use of medications that impact cefixime, azithromycin, or doxycycline metabolism (check versus list in screening SOP)

Primary outcomes:
measure: Number of participants with NG, CT, or early syphilis infection (combined STI outcome)
timeFrame: Over 18 months of follow-up at quarterly visits from the date of randomization
Secondary outcomes:
measure: Number of participants with Neisseria gonorrhea infection
timeFrame: Over 18 months of follow-up at quarterly visits from the date of randomization
measure: Number of participants with Chlamydia trachomatis infection
timeFrame: Over 18 months of follow-up at quarterly visits from the date of randomization
measure: Number of participants with early syphilis infection
timeFrame: Over 18 months of follow-up at quarterly visits from the date of randomization
Other outcomes:
measure: Number of gonorrhea infections with antimicrobial resistance mutations
timeFrame: Over 18 months of follow-up at quarterly visits from the date of randomization
measure: Acceptability of Intervention Measure
timeFrame: Measured every 6 months over 18 months of follow-up from the date of randomization
measure: Feasibility of Intervention Measure
timeFrame: Measured every 6 months over 18 months of follow-up from the date of randomization
measure: Adverse events
timeFrame: Over 18 months of follow-up at quarterly visits from the date of randomization
Locations:
Study officials:
affiliation: University of Washington
name: Susan M Graham, MD, PhD, MPH
role: PRINCIPAL_INVESTIGATOR
References: