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

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

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.

Study Overview

• Status: Completed
• Conditions: HIV Seropositivity
• Intervention / Treatment: Device: PrePex male circumcision device

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 430
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Zimbabwe
  • Harare
    • Chitungwiza, Harare, Zimbabwe
      • Zengeza Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HIV+ PrePex; PrePex male circumcision device	Device: PrePex male circumcision device; 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.

What is the study measuring?

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 hematomaPenis-wide diffuse edemaIncision site infection and related symptoms; Device-related incidentsNecrotic Process not initiatedDevice 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

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: Centers for Disease Control and Prevention; University of Zimbabwe; Ministry of Health and Child Welfare, Zimbabwe; Zimbabwe Community Health Intervention Research Project (ZiCHIRe), Zimbabwe
• Investigators: Principal Investigator: Scott Barnhart, MD, MPH, University of Washington

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2015
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: December 5, 2014
• First Submitted That Met QC Criteria: July 11, 2017
• First Posted (Actual): July 17, 2017

Study Record Updates

• Last Update Posted (Actual): July 17, 2017
• Last Update Submitted That Met QC Criteria: July 11, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: HIV Seropositivity; PrePex
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; HIV Seropositivity
• Other Study ID Numbers: STUDY00000126

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