Episodic Acyclovir Therapy for Genital Ulcers

Tracking Information
First Submitted Date ICMJE	September 9, 2005
First Posted Date ICMJE	September 14, 2005
Last Update Posted Date	September 11, 2012
Study Start Date ICMJE	March 2005
Actual Primary Completion Date	March 2009 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: September 10, 2005)	Ulcer healing
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT00164424 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: September 10, 2005)	HIV viral load from genital ulcers; HIV viral load in semen
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Episodic Acyclovir Therapy for Genital Ulcers
Official Title ICMJE	Impact of Episodic Acyclovir Therapy on Ulcer Duration and HIV Shedding From Genital Ulcers Among Men in South Africa
Brief Summary	The purpose of this study is to determine if acyclovir episodic treatment has an effect in ulcer healing and if it should be added to the syndromic management of genital ulcer disease.
Detailed Description	Background and Objectives: Herpes simplex virus type 2 (HSV-2) is the primary cause of genital ulcer and one of the most prevalent sexually transmitted infections (STI) worldwide. HSV-2 has been recognized as a risk factor for HIV in multiple studies. A substantial shift in the aetiology of genital ulcer disease (GUD) towards genital herpes has been noted in many countries in Africa, especially those with mature HIV epidemics. Some countries guided by the predominance of HSV-2 as the aetiology of GUD in their country, are changing syndromic guidelines to include acyclovir as part of the treatment for GUD. Little data is available to support this decision in terms of its effect on clinical course and its cost-effectiveness. Yet, substantial investment would be needed in poor countries to add acyclovir to their essential drug list. Studies to determine the appropriateness of episodic acyclovir therapy for HSV-2 in the developing world are needed. Episodic therapy with acyclovir both as a treatment modality and as an HIV-prevention strategy is appealing, in terms of cost and sustainability. However, it is not clear which will be its impact under field conditions in which there would be delay in symptom recognition and treatment initiation, and whether these conditions could be optimized through patient education. We propose to conduct a randomized placebo-controlled trial of the effect of HSV-2 episodic therapy on symptomatic herpes and on HIV shedding from genital ulcers. This study will help answer the question if acyclovir therapy for herpes should be added into the syndromic management of genital ulcer disease. Acyclovir has an acceptable profile for widespread STI treatment and is now relatively inexpensive and well-tolerated. Given that HSV-2 is the leading cause of GUD in the developing world, this approach could have great public health importance, by providing a safe, acceptable, and cost-effective method to treat genital ulcer disease and potentially reduce HIV transmission. If acyclovir therapy reduces HIV shedding, its incorporation into syndromic management would provide and effective way to scale it up as a public health intervention. Methods: We plan an individually randomized double blind placebo-control trial of the WHO and US CDC recommended dose of 3-times daily acyclovir for a 5-day treatment course. The trial will be conducted at two primary health care clinics in Johannesburg, South Africa. A total of 600 men presenting to the clinic with GUD will be enrolled in the study. Consenting participants will be randomized to receive either acyclovir plus syndromic management or placebo plus syndromic management. Syndromic management for genital ulcer disease will consist of one dose antibiotics to cover for syphilis and chancroid. Participants will be followed for a month; during follow-up visits duration of ulcers, ulcer number and size will be evaluated and ulcer, blood and semen samples collected to test for HIV RNA viral loads among HIV-positives and for HSV-2 shedding. Timeline: Duration of the project is 2 years Expected Outcomes: The main outcome of the study will be the evaluation of the impact of acyclovir therapy on ulcer healing. We will also measure the impact of acyclovir therapy on HIV and HSV-2 viral load from genital ulcers and HIV viral load in semen.
Study Type ICMJE	Interventional
Study Phase	Phase 2; Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double; Primary Purpose: Treatment
Condition ICMJE	HIV Infections; Ulcer; Herpes Simplex
Intervention ICMJE	Drug: Acyclovir
Study Arms	Not Provided
Publications *	Paz Bailey G, Sternberg M, Lewis DA, Puren A. Acute HIV infections among men with genital ulcer disease in South Africa. J Infect Dis. 2010 Jun 15;201(12):1811-5. doi: 10.1086/652785.; Paz-Bailey G, Sternberg M, Puren AJ, Markowitz LE, Ballard R, Delany S, Hawkes S, Nwanyanwu O, Ryan C, Lewis DA. Improvement in healing and reduction in HIV shedding with episodic acyclovir therapy as part of syndromic management among men: a randomized, controlled trial. J Infect Dis. 2009 Oct 1;200(7):1039-49. doi: 10.1086/605647.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: September 10, 2012)	613
Original Enrollment ICMJE; (submitted: September 10, 2005)	600
Actual Study Completion Date	July 2011
Actual Primary Completion Date	March 2009 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Males presenting at the primary health care clinic with a genital ulcer; Age 18 years or older; Willing and able to give informed consent; Willing to be tested for HSV and HIV; Willing and able to comply with the study protocol including follow-up visits; Willing to accept therapy by chance Exclusion Criteria: Extensive ulceration; Ulceration >1 month; History of adverse reaction to acyclovir; Taking suppressive therapy for genital herpes; History of renal insufficiency or proteinuria
Sex/Gender	Sexes Eligible for Study: Male
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	South Africa
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00164424
Other Study ID Numbers ICMJE	CDC-NCHSTP-4294
Has Data Monitoring Committee	Not Provided
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Centers for Disease Control and Prevention
Study Sponsor ICMJE	Centers for Disease Control and Prevention
Collaborators ICMJE	London School of Hygiene and Tropical Medicine; National Institute for Communicable Diseases, South Africa
Investigators ICMJE	Principal Investigator: Gabriela Paz Bailey, MD Centers for Disease Control and Prevention Principal Investigator: David Lewis, MD STIRC, National Institute for Communicable Diseases (NICD), South Africa
PRS Account	Centers for Disease Control and Prevention
Verification Date	September 2012
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP