Clinical Trials For Genital Herpes Episodic Acyclovir Therapy for Genital Ulcers

Episodic Acyclovir Therapy for Genital Ulcers

This study is currently recruiting participants.

Verified by Centers for Disease Control and Prevention, September 2005

First Received: September 9, 2005   Last Updated: October 20, 2005   History of Changes

Sponsor:

Centers for Disease Control and Prevention

Collaborators:

London School of Hygiene and Tropical Medicine

STI Reference Center, National Institute for Communicable Diseases, Johannesburg, South Africa

Information provided by:

Centers for Disease Control and Prevention

ClinicalTrials.gov Identifier:

NCT00164424

Purpose

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.


Condition

Intervention

Phase

HIV Infections

Ulcer

Herpes Simplex

Drug: Acyclovir

Phase II

Phase III


Study Type:

Interventional

Study Design:

Allocation: Randomized

Control: Placebo Control

Endpoint Classification: Efficacy Study

Intervention Model: Parallel Assignment

Masking: Double-Blind

Primary Purpose: Treatment

Official Title:

Impact of Episodic Acyclovir Therapy on Ulcer Duration and HIV Shedding From Genital Ulcers Among Men in South Africa


Resource links provided by NLM:


MedlinePlus related topics: AIDS Herpes Simplex

Drug Information available for: Acyclovir Acyclovir sodium

U.S. FDA Resources


Further study details as provided by Centers for Disease Control and Prevention:


Primary Outcome Measures:

Ulcer healing


Secondary Outcome Measures:

HIV viral load from genital ulcers

HIV viral load in semen


Estimated Enrollment:

600

Study Start Date:

March 2005

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.

Eligibility


Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Male

Accepts Healthy Volunteers:

No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00164424


Contacts

Contact: Gabriela Paz Bailey, MD

Tel: 502 236 Cell:502-55507104 ext 354

gpbz@cdc.gov

Contact: David Lewis, MD

Tel: 011 489 9491 Cell: 082 86

david.lewis@nhls.ac.za


Locations

South Africa, Gauteng

Eloff Street Clinic

Recruiting

Johannesburg, Gauteng, South Africa

Contact: Keletso Mmoledi, Sister     082 8878 675

Contact: Thuli Makhanya, Sister     082 8878 675

Green Door, Alexandra Health Centre

Recruiting

Johannesburg, Gauteng, South Africa

Contact: Joyce Lethoba, Sister     082 887 0279

Sponsors and Collaborators

Centers for Disease Control and Prevention

London School of Hygiene and Tropical Medicine

STI Reference Center, National Institute for Communicable Diseases, Johannesburg, South Africa

Investigators

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

More Information


No publications provided by Centers for Disease Control and Prevention


Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

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.

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.


ClinicalTrials.gov Identifier:

NCT00164424 History of Changes

Other Study ID Numbers:

CDC-NCHSTP-4294

Study First Received:

September 9, 2005

Last Updated:

October 20, 2005

Health Authority:

United States: Federal Government


Keywords provided by Centers for Disease Control and Prevention:

HSV2

genital ulcer

HIV

South Africa

Treatment

Acyclovir

Prevention


Additional relevant MeSH terms:

Herpes Simplex

Anti-Infective Agents

RNA Virus Infections

Sexually Transmitted Diseases, Viral

Slow Virus Diseases

Skin Diseases

Immune System Diseases

Ulcer

Acquired Immunodeficiency Syndrome

Antiviral Agents

Pharmacologic Actions

Immunologic Deficiency Syndromes

Herpesviridae Infections

Skin Diseases, Viral

Virus Diseases

Skin Diseases, Infectious

Acyclovir

Pathologic Processes

HIV Infections

Therapeutic Uses

Sexually Transmitted Diseases

Lentivirus Infections

DNA Virus Infections

Retroviridae Infections


ClinicalTrials.gov processed this record on June 15, 2010 Episodic Acyclovir Therapy for Genital Ulcers

This study is currently recruiting participants.

Verified by Centers for Disease Control and Prevention, September 2005

First Received: September 9, 2005   Last Updated: October 20, 2005   History of Changes

Sponsor:

Centers for Disease Control and Prevention

Collaborators:

London School of Hygiene and Tropical Medicine

STI Reference Center, National Institute for Communicable Diseases, Johannesburg, South Africa

Information provided by:

Centers for Disease Control and Prevention

ClinicalTrials.gov Identifier:

NCT00164424

Purpose

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.


Condition

Intervention

Phase

HIV Infections

Ulcer

Herpes Simplex

Drug: Acyclovir

Phase II

Phase III


Study Type:

Interventional

Study Design:

Allocation: Randomized

Control: Placebo Control

Endpoint Classification: Efficacy Study

Intervention Model: Parallel Assignment

Masking: Double-Blind

Primary Purpose: Treatment

Official Title:

Impact of Episodic Acyclovir Therapy on Ulcer Duration and HIV Shedding From Genital Ulcers Among Men in South Africa


Resource links provided by NLM:


MedlinePlus related topics: AIDS Herpes Simplex

Drug Information available for: Acyclovir Acyclovir sodium

U.S. FDA Resources


Further study details as provided by Centers for Disease Control and Prevention:


Primary Outcome Measures:

Ulcer healing


Secondary Outcome Measures:

HIV viral load from genital ulcers

HIV viral load in semen


Estimated Enrollment:

600

Study Start Date:

March 2005

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.

Eligibility


Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Male

Accepts Healthy Volunteers:

No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00164424


Contacts

Contact: Gabriela Paz Bailey, MD

Tel: 502 236 Cell:502-55507104 ext 354

gpbz@cdc.gov

Contact: David Lewis, MD

Tel: 011 489 9491 Cell: 082 86

david.lewis@nhls.ac.za


Locations

South Africa, Gauteng

Eloff Street Clinic

Recruiting

Johannesburg, Gauteng, South Africa

Contact: Keletso Mmoledi, Sister     082 8878 675

Contact: Thuli Makhanya, Sister     082 8878 675

Green Door, Alexandra Health Centre

Recruiting

Johannesburg, Gauteng, South Africa

Contact: Joyce Lethoba, Sister     082 887 0279

Sponsors and Collaborators

Centers for Disease Control and Prevention

London School of Hygiene and Tropical Medicine

STI Reference Center, National Institute for Communicable Diseases, Johannesburg, South Africa

Investigators

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

More Information


No publications provided by Centers for Disease Control and Prevention


Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

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.

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.


ClinicalTrials.gov Identifier:

NCT00164424 History of Changes

Other Study ID Numbers:

CDC-NCHSTP-4294

Study First Received:

September 9, 2005

Last Updated:

October 20, 2005

Health Authority:

United States: Federal Government


Keywords provided by Centers for Disease Control and Prevention:

HSV2

genital ulcer

HIV

South Africa

Treatment

Acyclovir

Prevention


Additional relevant MeSH terms:

Herpes Simplex

Anti-Infective Agents

RNA Virus Infections

Sexually Transmitted Diseases, Viral

Slow Virus Diseases

Skin Diseases

Immune System Diseases

Ulcer

Acquired Immunodeficiency Syndrome

Antiviral Agents

Pharmacologic Actions

Immunologic Deficiency Syndromes

Herpesviridae Infections

Skin Diseases, Viral

Virus Diseases

Skin Diseases, Infectious

Acyclovir

Pathologic Processes

HIV Infections

Therapeutic Uses

Sexually Transmitted Diseases

Lentivirus Infections

DNA Virus Infections

Retroviridae Infections


ClinicalTrials.gov processed this record on June 15