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

WHO-recommended Periodic Presumptive Treatment Versus Doxycycline Post-Exposure Prophylaxis for STI Control Among Cisgender Men Who Have Sex With Men in Kenya

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.

Study Overview

• Status: Recruiting
• Conditions: Gonorrhea Male; Chlamydia (Male); Syphilis Male
• Intervention / Treatment: Drug: WHO-recommended periodic presumptive treatment; Drug: Doxycycline post-exposure prophylaxis

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 Type: Interventional
• Enrollment (Estimated): 2900
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Susan M Graham, MD, PhD, MPH; Phone Number: +1-206-351-0414; Email: grahamsm@uw.edu
• Study Contact Backup: Name: Eduard J Sanders, MD, PhD, MPH; Phone Number: +254-723-593762; Email: esanders@auruminstitute.org

Study Locations

• Kenya
  • Kisumu, Kenya
    • Recruiting
    • Anza Mapema Clinic
    • Contact: Fredrick O Otieno, PhD MPH; Phone Number: 254572024065; Email: fotieno@nrhskenya.org
    • Contact: Carol Agwanda; Phone Number: 254725323274; Email: cagwanda@nrhskenya.org
    • Principal Investigator: Fredrick O Otieno, PhD MPH
  • Mombasa, Kenya
    • Recruiting
    • University of Washington/Pwani Research Centre at the Ganjoni Municipal Clinic, Mombasa
    • Contact: Eduard J Sanders, MD PhD; Phone Number: 254 723 593762; Email: ejs45@uw.edu
    • Contact: R. Scott McClelland, MD MPH; Phone Number: 2064730392; Email: mcclell@uw.edu
    • Principal Investigator: Eduard J Sanders, MD PhD
    • Sub-Investigator: R. Scott McClelland, MD MPH
  • Nairobi, Kenya
    • Recruiting
    • TRANSFORM Clinic
    • Contact: Joshua Kimani, MBChB, MPH; Phone Number: +254 20 210 1155; Email: Jkimani@phdaf.org
    • Contact: Rhoda W Kabuti, MBChB; Phone Number: +254 20 210 1155; Email: rwanjiru@phdaf.org
    • Principal Investigator: Joshua Kimani, MBChB MPH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	Drug: WHO-recommended periodic presumptive treatment; 400 mg po cefixime plus 1 gram azithromycin po under direct observation; Other Names: WHO PPT
No Intervention: Standard care; Participants assigned to the standard care arm will receive screening for STI symptoms at every scheduled visit and syndromic treatment with cefixime 400 mg po stat plus azithromycin 1 gram po stat under direct observation, in accordance with current Kenyan recommendations for genital and anorectal infections. This regimen will be updated if Kenyan recommendations change.
Active Comparator: 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.	Drug: Doxycycline post-exposure prophylaxis; 200 mg po doxycycline within 24-72 hours after condomless anal or vaginal sex as frequently as daily; Other Names: doxyPEP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with NG, CT, or early syphilis infection (combined STI outcome)	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.	Over 18 months of follow-up at quarterly visits from the date of randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Neisseria gonorrhea infection	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.	Over 18 months of follow-up at quarterly visits from the date of randomization
Number of participants with Chlamydia trachomatis infection	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.	Over 18 months of follow-up at quarterly visits from the date of randomization
Number of participants with early syphilis infection	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	Over 18 months of follow-up at quarterly visits from the date of randomization

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of gonorrhea infections with antimicrobial resistance mutations	The number of gonorrhea infections with genetic determinants conferring resistance to cefixime, azithromycin or tetracycline resistance will be determined a each visit	Over 18 months of follow-up at quarterly visits from the date of randomization
Acceptability of Intervention Measure	The Acceptability of Intervention Measure (4 questions rated from 0 to 4) will be assessed at baseline and every 6 months thereafter in all study arms. The "intervention" assessed will be the study arm to which the participant is assigned (i.e., presumptive treatment, doxyPEP, or standard care).	Measured every 6 months over 18 months of follow-up from the date of randomization
Feasibility of Intervention Measure	The Feasibility of Intervention Measure (4 questions rated from 0 to 4) will be assessed at baseline and every 6 months thereafter in all study arms. The "intervention" assessed will be the study arm to which the participant is assigned (i.e., presumptive treatment, doxyPEP, or standard care).	Measured every 6 months over 18 months of follow-up from the date of randomization
Adverse events	Number of adverse events, including social harms, reported by participants or study staff at each study visit	Over 18 months of follow-up at quarterly visits from the date of randomization

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); Aurum Institute; Nyanza Reproductive Health Society; Partners for Health & Development in Africa
• Investigators: Principal Investigator: Susan M Graham, MD, PhD, MPH, University of Washington

Study record dates

Study Major Dates

• Study Start (Actual): October 29, 2025
• Primary Completion (Estimated): October 31, 2028
• Study Completion (Estimated): April 30, 2029

Study Registration Dates

• First Submitted: June 1, 2024
• First Submitted That Met QC Criteria: June 15, 2024
• First Posted (Actual): June 21, 2024

Study Record Updates

• Last Update Posted (Actual): November 19, 2025
• Last Update Submitted That Met QC Criteria: November 16, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: syphilis; gonorrhea; chlamydia
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Infections; Communicable Diseases; Sexually Transmitted Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Negative Bacterial Infections; Spirochaetales Infections; Chlamydiaceae Infections; Sexually Transmitted Diseases, Bacterial; Neisseriaceae Infections; Treponemal Infections; Chlamydia Infections; Gonorrhea; Syphilis; Anti-Bacterial Agents; Anti-Infective Agents; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Doxycycline
• Other Study ID Numbers: STUDY00018588; 1R01AI179838-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

All data produced in the course of the project will be preserved and shared. The final dataset will include self-reported demographic and behavioral data from interviews with participants, clinical data from participant symptoms and focused physical exams, and laboratory data from blood and genitourinary specimens provided.

We will share de-identified individual-participant level data. Appropriate measures such as expert determination to identify for removal any specific variables that could potentially lead to identification of individuals. Plans for data de-identification and sharing will be reflected in the informed consent forms.

To facilitate interpretation of the data, a data dictionary describing all variables in the dataset, the study protocol, and all data collection instruments will be created, shared, and associated with the relevant datasets. Documentation and support materials will be compatible with the clinicaltrials.gov Protocol Registration Data Elements.

• IPD Sharing Time Frame: Data will be made available indefinitely from year 5 of the 5-year funded grant cycle.
• IPD Sharing Access Criteria: Due to ethical considerations, access, distribution, and reuse of the resulting scientific data will be limited to collaborations in which a formal data sharing agreement is developed and approved by the University of Washington and Kenyatta National Hospital Ethical Review Boards.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

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