A randomized placebo controlled trial of a combination of acyclovir, benzathine penicillin and ciprofloxacin versus a combination of placebo, benzathine penicillin and ciprofloxacin for the syndromic treatment of genital ulcer disease in Malawi

ISRCTN	ISRCTN32121857
DOI	https://doi.org/10.1186/ISRCTN32121857
Protocol serial number	04-MED-388
Sponsor	University of North Carolina (USA)
Funders	National AIDS Commission, Malawi Ministry of Health, Lilongwe, Malawi

Submission date: 27/09/2005
Registration date: 03/02/2006
Last edited: 26/06/2014

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Urological and Genital Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Mr Irving Hoffman
Scientific

Center for Infectious Diseases
1700 MLK Jr. Boulevard
Suite 129
CB# 3368
Chapel Hill
27599-3368
United States of America

Phone	+1 919 843 6324
Email	hoffmani@med.unc.edu

Study information

Primary study design	Interventional
Study design	Randomised controlled trial
Secondary study design	Randomised controlled trial
Scientific title
Study objectives	Control of Sexually Transmitted Infections (STI), including Genital Ulcer Disease (GUD), has been established as an important strategy for the prevention of Human Immunodeficiency Virus (HIV) transmission. Studies have shown that GUD causes an increase in the concentration of HIV-RNA (RiboNucleic Acid) in ulcer lesions and semen, which may increase HIV transmissibility, and which is reversible with GUD treatment. As recommended by the World Health Organization for resource poor countries, a syndromic approach to managing patients with genital ulcers is utilized in Malawi. Based on data from the early 1990s, the current syndromic management of GUD is designed to treat syphilis and chancroid only. More recent data from Lilongwe Central Hospital in Malawi, however, shows that as many as 35% of patients presenting to the Sexually Transmitted Disease (STD) clinic with GUD are infected with genital herpes. HIV seroprevalence rates are well over 50% among these genital ulcer patients. Although there is no cure for genital herpes, treatment with anti-herpetic agents can have a significant effect on its management. In addition, recent changes in the availability and price of selected anti-herpetic agents make it an affordable option for many countries as a component in the treatment of genital ulcers. Through a randomized double blinded, placebo controlled trial, this investigation will determine if adding the anti-herpetic agent, acyclovir, to the current syndromic management of GUD improves the cure rate of genital ulcers. In addition, it will determine whether treatment with acyclovir will affect the levels of HIV-RNA in the genital secretions and blood of men and women co-infected with HIV and Herpes Simplex Virus (HSV).
Ethics approval(s)	Not provided at time of registration
Health condition(s) or problem(s) studied	Genital Ulcer Disease (GUD)
Intervention	A combination of acyclovir, benzathine penicillin and ciprofloxacin versus a combination of placebo, benzathine penicillin and ciprofloxacin
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Acyclovir, benzathine penicillin, ciprofloxacin
Primary outcome measure(s)	1. To determine if the addition of acyclovir for the treatment of genital herpes will improve the cure rate of the current syndromic management for GUD in Malawi 2. To determine if HIV status affects this cure rate
Key secondary outcome measure(s)	1. To determine if GUD management, with and without treatment for genital herpes, affects the level of HIV-RNA in the blood, ulcer lesion as well as genital secretions of HIV-infected patients with GUD and whether this is related to cure rate 2. To assess the incremental cost benefit for the addition of acyclovir to the current syndromic treatment of GUD
Completion date	01/01/2006

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	500
Key inclusion criteria	1. Age 18 years or older 2. Clinically confirmed genital ulcer(s) 3. Ability to provide informed consent for participation, examination and sample collection 4. Willingness to be counselled 5. Tested and received results for HIV and other STIs 6. Resident in Lilongwe catchments area and with intention to stay for at least one month
Key exclusion criteria	1. Younger than 18 years old 2. Known allergy to penicillin, erythromycin, acyclovir, or ciprofloxacin 3. Patients with known or evidence of renal impairment 4. Very sick requiring admission 5. Women currently menstruating 6. Pregnant or lactating mothers
Date of first enrolment	01/09/2004
Date of final enrolment	01/01/2006

Locations

Countries of recruitment

Malawi
United States of America

Study participating centre

Center for Infectious Diseases

Chapel Hill
27599-3368
United States of America

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/12/2013		Yes	No