Evaluation of the PrePex Device for Rapid Scale-up of VMMC, Phase 3 Field Implementation Trial With HIV + Adult Males

Study Overview
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Brief Summary
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This study will assess the safety of the PrePex device as applied to HIV positive men by assessing the rate of clinical adverse events. The study will include adult, HIV + men who are eligible to receive the PrePex procedure per the Zimbabwe Ministry of Health and Child Care (MOHCC) eligibility criteria.

Detailed Description
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According to mathematical modeling, Voluntary Medical Male Circumcision (VMMC) has the potential to have a major impact on reducing HIV incidence in areas with high HIV prevalence and low prevalence of male circumcision, as is the case in Zimbabwe. Male circumcision devices have the potential to accelerate VMMC scale-up as the procedure is faster and simpler and can be safely performed by nurses. However, fear of social stigma and desire to avoid HIV testing remain potential barriers to those HIV+ men who would otherwise seek out VMMC. Study subjects (n=400) are HIV+ males who elect to undergo VMMC with PrePex as a study subject, and healthcare workers involved in implementation of PrePex on HIV+ male subjects. The aim of the study is to determine if PrePex can be used safely among HIV+ men with similar rates of adverse events to HIV-uninfected men. If so, then the barrier of mandatory HIV testing as part of VMMC could be removed, encouraging more men to undergo the procedure. Determining PrePex safety in HIV+ men would also allow both those with unknown status and those with positive status to undergo MC with PrePex. Determining the barriers to performing VMMC among HIV+ men among healthcare workers, if any, would also inform future policy.

Official Title
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Evaluation of Safety, Efficacy and Acceptability of the PrePexTM Device for Rapid Scale-up of Adult Male Circumcision Programs in Zimbabwe, Phase III PrePexTM Field Implementation Trial With HIV Positive Adult Males

Conditions
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HIV Seropositivity

Intervention / Treatment
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* Device: PrePex male circumcision device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Agrees to take an HIV test HIV sero-positive WHO HIV clinical stage 1 or 2 Age 18 years and above Agrees to be circumcised by PrePex Able to understand the study procedures and requirements Completes VMMC counseling Agrees to return to the health care facility for follow-up visits or as instructed after this circumcision until complete healing 7 weeks from device application, or until cleared by a physician Able to comprehend and freely give informed consent for study participation Exclusion Criteria: Known bleeding/coagulation abnormality (excessive bleeding from nosebleeds, pulled tooth, or gums) Uncontrolled diabetes (frequent treatment in a clinic or recent hospitalization for diabetes, frequent infections, hypertension, or kidney disease) Active genital infection, anatomic abnormality or any other condition, which in the opinion of the investigator prevents the subject from undergoing circumcision using PrePex. HIV sero-negative HIV status unknown WHO HIV stage 3 and above Does not agree to PrePex

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Intervention Model: Single Group Assignment
Interventional Model Description: The study is a one arm, open label, prospective, cohort field study to assess the safety and acceptability of PrePex device circumcision device when performed by certified PrePex circumcision providers (physicians & nurses) in a HIV-infected male population.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HIV+ PrePex<br>PrePex male circumcision device | Device: PrePex male circumcision device<br>* PrePex non-surgical male circumcision device applied to eligible, consenting HIV-infected men in Zimbabwe to determine the rate of adverse events as compared to non HIV-infected men.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of adverse events among HIV+ males using PrePex device | The primary safety endpoint is the incidence of clinical adverse events and device-related incidents. Clinical related incidents such as the following: Site bleeding (bleeding that cannot be stopped with pressure of 30 seconds and requires suturing) Penis-wide diffuse hematoma Penis-wide diffuse edema Incision site infection and related symptoms Device-related incidents Necrotic Process not initiated Device does not remain in situ for the full 7 days (displacement) Note: This list of AEs is not exhaustive. Severity of AE will be determined according to PEPFAR/OGAC guidelines | Device application through complete wound healing (up to 90 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain assessment at key time points | Subject's subjective pain, tingling, and discomfort related to PrePex when applying the system, wearing it and removing it. This will be assessed by numeric pain, tingling and discomfort VAS scale (Pain = VAS x Duration in Minutes). Measured in the post placement recovery at 15 minutes after placement, and then 1, 2, and 3 hours post placement. As the necrotic process initiates, it is expected that some of subjects will have temporary discomfort during the first 2 hours after deployment (hence anaesthetic cream), which vanishes thereafter for the rest of the weeklong period when the device is in place. Some pain is expected for a short duration (about 10 seconds) when extracting the Inner Ring during the removal procedure. | Placement through complete healing (up to 90 days) | 
| Abstinence until complete wound healing | Survival analysis of the timing of resumed sexual activity among subjects | Post placement through complete healing (up to 90 days) | 
| Factors associated with abstinence until complete wound healing | Patient factors (knowledge, attitudes) associated with abstinence from sex until wound healing is complete | Post placement through complete healing (approximately 90 days for men who participate in the qualitative component) | 
| Time to complete healing | Mean of days for complete healing (continuous measure) and factors associated with number of days to complete healing (continuous outcome - multiple linear regression) A completely healed circumcision as defined as, Intact epithelium (unbroken skin) covering the epithelial as judged by the provider on visual inspection, meaning that none of the following are present: sutures, scabbing, drainage, moisture, gaps between epithelial edges or ulceration.] Optional validation by objective analysis of wounds by photographs | Device placement through complete healing (up to 90 days) | 
| Cosmetic results | Objective analysis of photographs Glans fully exposed (complete circumcision) | At complete healing (up to 90 days) | 
| Patient satisfaction | A composite measure created among patients involved in the qualitative component who will be asked about satisfaction with the PrePex™ MC procedure, barriers and motivators to uptake of VMMC through PrePex™, opinions around convenience of the device, tolerance of potential odour and whether participants would recommend PrePex™ MC to others. | 3 time points: Prior to the procedure, two weeks post-procedure, and 90 days post-procedure Device placement through  90 days post procedure | 
| Patient daily life | Patients involved in the qualitative component will be asked about activities of daily living restrictions. They will complete a brief form that includes listing of activities of daily living, whether they are interrupted and for how long. This includes the average number of lost working hours (or potential working hours in unemployed). A composite measure will be created. | 3 time points: Prior to the procedure, two weeks post-procedure, and 90 days post-procedure Device placement through  90 days post procedure | 
| PrePex staff perceptions | Responses by clinicians to Likert scale questions on their beliefs about PrePex VMMC and using this procedure on HIV+ men | 4 weeks after study implementation begins | 
| PrePex staff clinical skills | An overall assessment of clinician skills as a group will be made by combining and reporting on several indirect measures. Included measures will be the proportion of clients experiencing AEs and the average procedure time. • Assessing AE monitoring and reporting systems through completeness of reporting timeliness | At study closing,approximately 18 months after study initiation | 
| PrePex AE monitoring and reporting systems | An ongoing assessment of AE monitoring and reporting systems through completeness of reporting timeliness of reports | During all active follow-up: 90 days for participants | 
| PrePex staff perceptions of their clinical skills | Compilation report of Likert scale results from questions ascertaining PrepPex training, abilities, productivity and confidence. | 4 weeks after study implementation begins | 
| PrePex staff satisfaction | Compilation report on responses to likert scales question on their satisfaction performing PrePex on HIV+ men. | 4 weeks after study implementation begins | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PrePex, HIV Seropositivity