The purpose of this study is to determine if azithromycin, a drug approved for treatment of other infections, is as effective for syphilis (a sexually transmitted disease) as the standard treatment. Approximately 600 healthy adults, who are HIV-negative, ages 18 to 55 years of age, with primary, secondary or early latent syphilis, will participate in this research study. Volunteers will be enrolled in 5 U.S. cities and in Madagascar. Participants will be chosen randomly (by chance) to receive 1 of 2 study drugs: benzathine penicillin given (2 shots in the buttocks) or 4 tablets of azithromycin. Subjects who report a history of a penicillin allergy will be given either 2.0 g of oral azithromycin or 100 mg doxycycline taken orally, twice a day for 14 days. Over 2 years, 10 visits will be required. Procedures will include blood samples, physical exams, and swabs of sores.
Drug: Benzathine Penicillin
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase III Equivalence Trial of Azithromycin vs. Benzathine Penicillin for the Treatment of Early Syphilis|
- Cure of syphilis defined as a negative reactive serologic test for syphilis (RPR) titer or greater than or equal to a 4-fold (2 dilution) decrease in RPR titer at 6 months following treatment and resolution of all signs and symptoms of syphilis. [ Time Frame: Month 6. ] [ Designated as safety issue: No ]
- Cure rates at 9, 12 and 24 months post treatment and the rate of relapse or reinfection defined as cure followed by recurrent clinical manifestations or a 2-dilution increase in RPR titer over previous lowest result. [ Time Frame: Months 9, 12, and 24. ] [ Designated as safety issue: No ]
|Study Start Date:||June 2000|
|Study Completion Date:||March 2009|
|Primary Completion Date:||August 2007 (Final data collection date for primary outcome measure)|
Azithromycin 2.0 gram single oral dose.
Single 2 gram oral dose (4 tablets) at Day 1.
Active Comparator: Benzathine Penicillin
Benzathine penicillin 2.4 million units administered intramuscularly. Doxycycline will be administered if the patient is allergic to Benzathine Penicillin.
Drug: Benzathine Penicillin
Supplied in pre-filled syringes containing 1.2 million units of benzathine penicillin; 2.4 million units administered intramuscularly at Day 1, in one or both buttocks.Drug: Doxycycline
Baseline visit, 28 capsules dispensed, for a dose of 100 mg twice a day (BID).
Syphilis is a disease with a worldwide distribution. It causes genital ulceration, thereby amplifying risk for HIV acquisition and transmission and it may cause congenital infection, spontaneous abortion, and stillbirth if untreated in pregnant women. About one third of all cases, if untreated, result in late sequelae which include neurosyphilis, gumma formation and cardiovascular involvement. This study will be a multi-center, randomized, open-label trial to evaluate the efficacy of azithromycin in treating primary, secondary and early latent syphilis in HIV (Human Immunodeficiency Virus) uninfected volunteers. Up through version 6.0 of this protocol volunteers were only followed for 12 months. The protocol was amended starting with version 7.0 to include follow-up visits at month 18 and 24 in order to capture possible "late failures." Each subject will be randomized into a treatment group. If the subject does not have a self-reported history of penicillin allergy, the subject will be randomized to receive either a single 2.0 gram dose of azithromycin administered orally, or 2.4 million units of benzathine penicillin G administered intramuscularly once. Eligible patients who report a history of penicillin allergy will be randomized (using a separate randomization schedule) to receive either a single dose of azithromycin or doxycycline, 100 milligrams, taken orally, twice a day for 14 days. Block randomization will be used within each clinical center with subjects allocated in equal numbers to either standard therapy or azithromycin. Participants found to be ineligible for study participation after they have been randomized and treated, will be treated again with benzathine penicillin G (or doxycycline if they are allergic to penicillin) and will continue follow-up for safety evaluation. The treatment assignments will not be blinded. No attempt will be made to recruit a sufficient sample size among penicillin allergic subjects to attain the desired power for the primary outcome. Therefore these results will be seen as preliminary to a possible future trial and as confirmatory to the primary comparison. Although the study endpoint will be determined at 6 months, all participants, will have follow-up visits for 2 full years. At the end of the 6 month evaluation period, all participants will have been classified in one of the following groups: cure; clinical response/serological nonresponse; or failure.
|United States, Alabama|
|University of Alabama Hospital - Infectious Diseases|
|Birmingham, Alabama, United States, 35249-0001|
|United States, Indiana|
|Indianapolis, Indiana, United States, 46202|
|United States, Louisiana|
|Louisiana State University Health Sciences Center - Infectious Diseases|
|New Orleans, Louisiana, United States, 70112-2865|
|United States, Maryland|
|Johns Hopkins Hospital - Medicine - Infectious Diseases|
|Baltimore, Maryland, United States, 21287-0005|
|United States, North Carolina|
|University of North Carolina at Chapel Hill|
|Chapel Hill, North Carolina, United States, 27514|
|University of North Carolina School of Medicine - Center for Infectious Diseases|
|Chapel Hill, North Carolina, United States, 27599-7030|
|Durham County Health Department|
|Durham, North Carolina, United States, 27701-3720|
|Laboratoire National de Reference sur le VIH/SIDA (LNR)|
|Analamanga, Antananarivo, Madagascar, 101|
|Tamatave, Antsiranana, Madagascar|
|Mahajanga Majunga, Mahajanga, Madagascar, 401|