Syphilis Response to Higher Penicillin Dosage: The 2.4 Versus 7.2 Study

Phase 4

Completed

• Conditions: Syphilis
• Interventions: Drug: Benzathine penicillin G intramuscular 2.4 million units; Drug: Benzathine penicillin G intramuscular 7.2 million units

• Registration Number: NCT02611765
• Lead Sponsor: Baylor College of Medicine

Brief Summary

Syphilis remains a significant health problem worldwide, with an estimated 10.6 million new cases per year. Due to shared transmission route and risk factors, co-infection with syphilis and Human Immunodeficiency Virus (HIV) is not uncommon. Several studies have evaluated the response to syphilis treatment in HIV-infected patients. They support the claim that patients with HIV have a slower decrease in syphilis antibody titers, and that they may progress to neurosyphilis in earlier stages.

The Center for Disease Control and Prevention's Sexually Transmitted Disease Treatment Guidelines has advocated treating HIV-infected patients who have primary, secondary syphilis or early latent syphilis with the same doses of penicillin as for HIV-uninfected patients (single dose of 2.4 million units of benzathine penicillin G). The investigators designed a randomized controlled trial in order to compare the efficacy of three- versus single-dosed regimens of intramuscular benzathine penicillin G (BPG) for the treatment of early syphilis in HIV-infected patients.

Detailed Description

The investigators conducted a prospective, randomized, open label study at three clinical sites including Thomas Street Health Center and North West Clinic (Harris Health System), and the Michael E. DeBakey Veterans Affairs Medical Center in Houston, Texas. After obtaining written informed consent, the investigators randomly assigned patients to either a single intramuscular injection of 2.4 million units of BPG (standard therapy) or three doses (enhanced therapy) of intramuscular BPG administered weekly (a total of 7.2 million units).

Patients were eligible for inclusion in the study if they were 18 years of age or older and had a diagnosis of HIV. The diagnosis of syphilis was made based on a positive Rapid Plasma Reagin (RPR) and treponema pallidum particle agglutination tests. Patients with primary, secondary and early latent syphilis were included.

Exclusion criteria were history of penicillin allergy, diagnosis of late latent syphilis, neurosyphilis, and antibiotic use with significant activity against Treponema pallidum within the preceding two weeks.

Follow-up period was 12 months. Serum samples were obtained at initial visit and follow-up visits every 3 months for serological testing for syphilis. Treatment success was defined as a decrease in RPR titer of \>= 2 dilutions (4-fold) from the initial RPR titer during the follow-up period.

Both intention-to-treat and per-protocol analyses were performed

Basic Information
|
Recruitment & Eligibility
|
Study & Design

Study Timeline

• Study Start: 2008-09
• Primary Completion: 2012-04
• Study Completion: 2012-04
• Study First Submitted: 2015-11-19
• Study First Submitted QC: 2015-11-20
• Study First Posted: 2015-11-23
• Results First Submitted: 2016-03-10
• Results First Submitted QC: 2016-03-10
• Status Verified: 2016-04
• Results First Posted: 2016-04-11
• Last Update Submitted: 2016-04-15
• Last Update Posted: 2016-05-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 64

Inclusion Criteria

• Diagnosed with HIV by ELISA and confirmed by Western blot
• Positive Rapid Plasma Reagin and treponema pallidum particle agglutination tests

Read More

Exclusion Criteria

• History of penicillin allergy
• Diagnosis of late latent syphilis
• Diagnosis of neurosyphilis
• Antibiotic use with significant activity against Treponema pallidum within the preceding two weeks

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard therapy	Benzathine penicillin G intramuscular 2.4 million units	Benzathine penicillin G intramuscular 2.4 million units A single intramuscular injection of 2.4 million units of benzathine penicillin G
Enhanced therapy	Benzathine penicillin G intramuscular 7.2 million units	Benzathine penicillin G intramuscular 7.2 million units Three doses of 2.4 million units of intramuscular benzathine penicillin G administered weekly (a total of 7.2 million units)

Primary Outcome Measures

Name	Time	Method
Treatment Success Defined as a Decrease in Rapid Plasma Reagin (RPR) Titer of >= 2 Dilutions (4-fold)	12 months	Number of participants who achieve treatment success. Loss to follow-up was assumed to be a failure.