Azithromycin/Bicillin Syphilis

NCT00031499 | Completed Phase 3

• 1 other identifier: 99-005
• Study Type: interventional
• Target: 593
• Locations: 2 countries
• Sites: 10

Brief Summary

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.

Conditions

Syphilis

Keywords

Azithromycin, Syphilis, Penicillin

Outcome Measures

Primary Outcomes (1)

• 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.

  Month 6.

Secondary Outcomes (1)

• 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.

  Months 9, 12, and 24.

Study Arms (2)

Azithromycin

EXPERIMENTAL

Azithromycin 2.0 gram single oral dose.

Drug: Azithromycin

Benzathine Penicillin

ACTIVE COMPARATOR

Benzathine penicillin 2.4 million units administered intramuscularly. Doxycycline will be administered if the patient is allergic to Benzathine Penicillin.

Drug: Benzathine Penicillin; Drug: Doxycycline

Interventions

Azithromycin DRUG

Single 2 gram oral dose (4 tablets) at Day 1.

Azithromycin

Benzathine Penicillin DRUG

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.

Benzathine Penicillin

Doxycycline DRUG

Baseline visit, 28 capsules dispensed, for a dose of 100 mg twice a day (BID).

Benzathine Penicillin

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• The subject is 18 to 55 years of age.
• The subject has signed written informed consent.
• The subject has untreated primary \[darkfield or Treponema (T.) pallidum by a rapid, direct, fluorescent antibody darkfield (DFA-TP)\] positive genital ulcers, secondary (based on classical palmar/plantar rash, condylomata lata, mucous patches, etc. or darkfield or DFA-TP positive lesions), or early latent syphilis (e.g., current reactive serologic tests for syphilis (STS), and a documented non-reactive STS or documented sexual exposure to a known early latent, primary or secondary syphilis patient in last 12 months; identification of this sexual contact must occur within 60 days of admission into the study).
• The subject has laboratory evidence of syphilis, i.e., reactive serologic test for syphilis (RPR).
• The subject is not pregnant, as documented by a negative urine or serum pregnancy test, or lactating.
• The subject is willing to have an HIV test, and, participate in HIV counseling and return to the clinic for follow-up treatment.

You may not qualify if:

• The subject does not have reactive serologic tests for syphilis.
• The subject has latent syphilis of unknown duration, late latent syphilis or evidence of neurosyphilis.
• The subject has a known or suspected allergy to macrolide or azalide antibiotics.
• The subject has a known or suspected sexually transmitted disease (STD), other than syphilis requiring treatment with a drug, other than azithromycin, active against T. pallidum.
• The subject has used antibiotics active against T. pallidum in the preceding 30 days. (Note: the use of antimicrobials known to NOT be effective against T. pallidum such as quinolones, sulfonamides, trimethoprim, metronidazole and spectinomycin will be allowed).
• The subject is known to be HIV positive prior to enrollment.
• The subject has suspected or known ongoing drug use that might interfere with study participation and follow-up treatment.
• The subject has a history of cardiovascular disease, known immunosuppression, or known AIDS, which might compromise response to therapy.
• The subject is judged by the investigators to be unlikely to reliably participate in the study follow-up.
• The subject has used any investigational drugs in the past 30 days.
• The subject has any other condition that may impair drug absorption (malabsorption syndrome or active peptic ulcer disease).

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (10)

University of Alabama Hospital - Infectious Diseases

Birmingham, Alabama, 35249-0001, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Louisiana State University Health Sciences Center - Infectious Diseases

New Orleans, Louisiana, 70112-2865, United States

Location

Johns Hopkins Hospital - Medicine - Infectious Diseases

Baltimore, Maryland, 21287-0005, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

University of North Carolina School of Medicine - Center for Infectious Diseases

Chapel Hill, North Carolina, 27599-7030, United States

Location

Durham County Health Department

Durham, North Carolina, 27701-3720, United States

Location

Laboratoire National de Reference sur le VIH/SIDA (LNR)

Analamanga, Antananarivo, 101, Madagascar

Location

Hopitaly Kely

Toamasina, Antsiranana, Madagascar

Location

Hopitaly Mahabibo

Mahajanga Majunga, Mahajanga, 401, Madagascar

Location

Related Publications (2)

• Sena AC, Wolff M, Martin DH, Behets F, Van Damme K, Leone P, Langley C, McNeil L, Hook EW. Predictors of serological cure and Serofast State after treatment in HIV-negative persons with early syphilis. Clin Infect Dis. 2011 Dec;53(11):1092-9. doi: 10.1093/cid/cir671. Epub 2011 Oct 12.

  PMID: 21998287 RESULT

• Hook EW 3rd, Behets F, Van Damme K, Ravelomanana N, Leone P, Sena AC, Martin D, Langley C, McNeil L, Wolff M. A phase III equivalence trial of azithromycin versus benzathine penicillin for treatment of early syphilis. J Infect Dis. 2010 Jun 1;201(11):1729-35. doi: 10.1086/652239.

  PMID: 20402591 RESULT

MeSH Terms

Conditions

Syphilis

Interventions

Azithromycin; Penicillin G Benzathine; Doxycycline

Condition Hierarchy (Ancestors)

Treponemal Infections; Spirochaetales Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Sexually Transmitted Diseases, Bacterial; Sexually Transmitted Diseases; Communicable Diseases; Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2002
• First Posted: March 7, 2002
• Study Start: June 1, 2000
• Primary Completion: August 1, 2007
• Study Completion: March 1, 2009
• Last Updated: April 29, 2013

Record last verified: 2013-04

Locations

US (7); MA (3)