Chlamydia (Male), Gonorrhea Male, Syphilis Male
Conditions
Keywords
gonorrhea, chlamydia, syphilis
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.
Interventions
DRUGWHO-recommended periodic presumptive treatment
400 mg po cefixime plus 1 gram azithromycin po under direct observation
DRUGDoxycycline post-exposure prophylaxis
200 mg po doxycycline within 24-72 hours after condomless anal or vaginal sex as frequently as daily
Sponsors
Aurum Institute
Nyanza Reproductive Health Society
National Institute of Allergy and Infectious Diseases (NIAID)
Partners for Health & Development in Africa
University of Washington
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Outcomes Assessor)
Masking description
Aptima Combo 2 testing for NG and CT will be conducted in Mombasa on a Hologic Panther platform by experienced laboratory staff blinded to randomization assignment.
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.
Eligibility
Sex/Gender
MALE
Age
18 Years to 29 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of gonorrhea infections with antimicrobial resistance mutations | Over 18 months of follow-up at quarterly visits from the date of randomization | The number of gonorrhea infections with genetic determinants conferring resistance to cefixime, azithromycin or tetracycline resistance will be determined a each visit |
| Acceptability of Intervention Measure | Measured every 6 months over 18 months of follow-up from the date of randomization | 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). |
| Feasibility of Intervention Measure | Measured every 6 months over 18 months of follow-up from the date of randomization | 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). |
| Adverse events | Over 18 months of follow-up at quarterly visits from the date of randomization | Number of adverse events, including social harms, reported by participants or study staff at each study visit |
Countries
Kenya
Contacts
Primary ContactSusan M Graham, MD, PhD, MPH
Backup ContactEduard J Sanders, MD, PhD, MPH
Outcome results
None listed