Periodic Presumptive Treatment vs. doxyPEP for STI Control in Kenyan MSM

Phase 4

Not yet recruiting

• Conditions: Chlamydia (Male); Syphilis Male; Gonorrhea Male
• Interventions: Drug: WHO-recommended periodic presumptive treatment; Drug: Doxycycline post-exposure prophylaxis

• Registration Number: NCT06468462
• Lead Sponsor: University of Washington

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.

Study Timeline

• Study First Submitted: 2024-06-01
• Study First Submitted QC: 2024-06-15
• Study First Posted: 2024-06-21
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-13
• Last Update Posted: 2024-10-16
• Study Start: 2024-12-01
• Primary Completion: 2028-01-31
• Study Completion: 2028-07-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Male
• Target Recruitment: 2900

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

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
WHO-recommended periodic presumptive treatment	WHO-recommended periodic presumptive treatment	Participants assigned to the STI PPT arm will be evaluated at baseline and every 3 months thereafter for STI PPT eligibility based on having had condomless anal sex and either multiple sex partners or a sex partner with an STI in the past 6 months. If eligible, they will be offered 400 mg po cefixime plus 1 gram azithromycin po under direct observation, using the same regimen as for syndromic treatment per the latest WHO recommendations.
Doxycycline post-exposure prophylaxis	Doxycycline post-exposure prophylaxis	Participants assigned to the doxyPEP arm will be provided with a 30-day supply of doxycycline hyclate at each quarterly visit, with refills as needed. They will have 1:1 counselling on the self-administration of 200 mg po doxycycline within 24-72 hours after condomless anal or vaginal sex as frequently as daily if indicated but not more than once daily, in accordance with the doxyPEP trial in the United States.

Primary Outcome Measures

Name	Time	Method
Number of participants with NG, CT, or early syphilis infection (combined STI outcome)	Over 18 months of follow-up at quarterly visits from the date of randomization	The number of participants with the combined STI outcome will be determined at each visit. The combined STI outcome will be positive when any Aptima test on a pooled specimen (throat, rectal, and urine) is positive for CT or NG or any participant tests positive for early syphilis infection, defined as a positive rapid plasma reagin \[RPR\] in a previously negative participant or a fourfold increase in non-treponemal titres for participants with a history of syphilis.

Secondary Outcome Measures

Name	Time	Method
Number of participants with Neisseria gonorrhea infection	Over 18 months of follow-up at quarterly visits from the date of randomization	The number of participants with an Aptima test on a pooled specimen (throat, rectal, and urine) positive for NG will be determined at each visit.
Number of participants with Chlamydia trachomatis infection	Over 18 months of follow-up at quarterly visits from the date of randomization	The number of participants with an Aptima test on a pooled specimen (throat, rectal, and urine) positive for CT will be determined at each visit.
Number of participants with early syphilis infection	Over 18 months of follow-up at quarterly visits from the date of randomization	The number of participants with early syphilis infection, defined as a positive rapid plasma reagin \[RPR\] in a previously negative participant or a fourfold increase in non-treponemal titres for participants with a history of syphilis, will be determined at each visit