Clinical trial NCT00971958: Infant Male Circumcision in Gaborone, Botswana, and Surrounding Areas: Feasibility, Safety and Acceptability
Official title: Infant Male Circumcision in Gaborone, Botswana, and Surrounding Areas: Feasibility, Safety and Acceptability
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV Infections
Circumcision
Keywords: HIV prevention
infant, neonatal, male circumcision
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2009-09-04
Enrollment: 1235
Sex: MALE
Maximum age (years): 28
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: Background: Novel HIV prevention approaches are urgently needed in Botswana and elsewhere in sub-Saharan Africa. Although adult male circumcision (MC) has been shown to reduce the heterosexual acquisition of HIV by men by about 60%, MC in infancy is optimal for its relative ease, lower cost and low rate of complications. We have conducted focus groups and semi-structured interviews that suggest neonatal MC (\< 28 days of life) would be an acceptable public HIV prevention strategy in Botswana. The government of Botswana is committed to scaling up MC services in the immediate future and they plan to include neonates. Understanding decision-making around infant MC will be essential to maximize the effectiveness of this HIV prevention strategy.

Specific Aims: The investigators propose to: 1) determine the acceptability and actual uptake of neonatal MC in southeastern Botswana and identify barriers to uptake; 2) ascertain the feasibility and safety of neonatal MC in Botswana; 3) Estimate what, if any, advantages would exist for scale up of Mogen Clamp, Plastibell or AccuCirc with regard to human resources, equipment needs, adverse events and acceptability to health-care providers and families in Botswana.

Study Design and Schema: The investigators will conduct structured interviews with early postpartum mothers and fathers to determine correlates of neonatal MC acceptability and uptake, defined as neonatal MC following informed consent. Male infants will be circumcised by a trained doctor in a hospital / clinic setting by one of three FDA-approved devices that are currently in use in US hospitals: Mogen clamp, Plastibell or AccuCirc. Circumcision with Mogen Clamp or Plastibell will be done before 29 days of life. Circumcision with AccuCirc will be done before 11 days of life (FDA approval limit for device). The investigators will also administer questionnaires to the parents at the regular pediatric follow-up visit(s) to assess impressions of / satisfaction with the infant's procedure outcome over time. Provider impressions of the three methods will also be evaluated. Sample size will be 150 infants per arm for a total of 450 infants males circumcised (and an estimated 800 parental questionnaires).

Public Health Significance: The World Health Organization (WHO) and UNAIDS state that countries with severe, generalized HIV epidemics but low rates of MC should offer this surgery as an important, evidence-based HIV prevention intervention, including among neonates. These two agencies also recommended that additional research on the most feasible, safe, and sustainable ways of scaling up MC intervention should be performed. This study will be in keeping with these recommendations.

Please note the Mogen clamp and Plastibell study arms began as a randomized trial before the initiation of the AccuCirc single-arm portion. Although the settings in which the three devices were studied were similar, the AccuCirc trial enrollment began at two sites (Gaborone and Molepolole) only after completion of the Mogen clamp and Plastibell arms, which was conducted in three sites (Gaborone, Molepolole and Mochudi). Although Lobatse was a site for the first acceptability study with mothers, no procedures were performed there.

Regarding the reported sample size: the total, final sample size includes both parents of newborn boys (because enrolled consenting parents completed questionnaires as part of this study), and boys whose parents consented to circumcision. We anticipated that not all parents who completed the questionnaire would consent to circumcising their baby; therefore, when planning the study it was necessary to estimate the number of parents who would participate in the survey (700), to achieve an enrollment of 300 neonates (therefore the initial estimate of 1000). The original study in fact enrolled 302 infants, 600 mothers and 19 fathers (total study population 921). The addition of the AccuCirc arm led to a revised estimate of total number of neonates and their parents (total=1250). The final enrollment was of 1,235 participants, that includes all the participating neonates and parents.


Eligibility criteria: Inclusion Criteria:

* Mothers (and fathers) of liveborn male infants at one of the four study sites who are \> 21 years of age (mothers less than 21 years of age, age of majority in Botswana, will provide assent, and will need consent from a guardian to allow participation of mother and infant in this study).
* Fathers of liveborn male infants at one of the four study sites who are \> 21 years of age
* Ability to follow up regularly at study clinic until 4 months postpartum
* Provision of written informed consent

Exclusion Criteria:

* Neonatal sepsis or other severe illness requiring infant hospitalization
* Penile abnormality that might require reconstructive surgery in the future (penile torsion / median raphe not midline, hypospadias / blind urethral pit, buried penis, penile-scrotal web, hydrocoele, dorsal hood / ventral foreskin missing, lack of scrotal ruggae suggesting lack of testicles bilaterally as could be karyotypic XX, megameatus or any other abnormality that may require consultation with urologist)
* Family history of bleeding disorder
* Estimated infant gestational age \< 37 weeks
* Infant delivery weight \< 2,500 grams
* Infant \> 4 weeks of age
* Infant receipt of methaemoglobin-inducing agents
* Current involuntary incarceration of mother

Primary outcomes:
measure: Adverse events that were potentially related to neonatal MC were defined prior to study initiation and categorized as bleeding, infection, structural and other.
timeFrame: Within 6 weeks
measure: Parental Satisfaction
timeFrame: At 6 weeks and 4 months
Secondary outcomes:
measure: Staff impressions of the comparative safety, tolerability, and ease of use of the techniques (Mogen Clamp and Plastibell only).
timeFrame: After 4 months
Other outcomes:
Locations:
city: Gaborone, Mochudi, Molepolole and Lobatse
country: Botswana
facility: Botswana-Harvard Partnership
Study officials:
affiliation: Brigham and Women's Hospital
name: Rebecca M. Plank, MD
role: PRINCIPAL_INVESTIGATOR
References: