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

Gonorrhea Male Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06468462
• Other study ID #: STUDY00018588
• Secondary ID: 1R01AI179838-01
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: August 1, 2024
• Est. completion date: July 30, 2028

Study information

• Verified date: June 2024
• Source: University of Washington
• Contact: Susan M Graham, MD, PhD, MPH
• Phone: +1-206-351-0414
• Email: grahamsm[@]uw.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 2900
• Est. completion date: July 30, 2028
• Est. primary completion date: January 31, 2028
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 29 Years

Eligibility

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)

• Receipt of Bexero meningococcal group B vaccine

Related Conditions & MeSH terms

• Chlamydia Infections
• Gonorrhea
• Gonorrhea Male
• Syphilis

Intervention

Drug:
• WHO-recommended periodic presumptive treatment
400 mg po cefixime plus 1 gram azithromycin po under direct observation
• Doxycycline post-exposure prophylaxis
200 mg po doxycycline within 24-72 hours after condomless anal or vaginal sex as frequently as daily

Locations

Country	Name	City	State
n/a

Sponsors (5)

Lead Sponsor	Collaborator
University of Washington	Aurum Institute, National Institute of Allergy and Infectious Diseases (NIAID), Nyanza Reproductive Health Society, Partners for Health and Development in Africa

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Primary	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	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
Secondary	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
Secondary	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