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

• Sponsor: Baylor College of Medicine (Other)
• Overall Status: Completed
• CT.gov ID: NCT02611765
• Collaborator: (none)
• Enrollment: 64
• Arms: 2
• Duration (Months): 43

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Syphilis	Drug: Benzathine penicillin G intramuscular 7.2 million units; Drug: Benzathine penicillin G intramuscular 2.4 million units	Phase 4

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Syphilis Response to Higher Penicillin Dosage in HIV Co-Infected Patients
• Study Start Date: Sep 1, 2008
• Actual Primary Completion Date: Apr 1, 2012
• Actual Study Completion Date: Apr 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Enhanced therapy 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)	Drug: Benzathine penicillin G intramuscular 7.2 million units; Three doses of intramuscular 2.4 million units of benzathine penicillin G administered weekly (a total of 7.2 million units).; Other Names: Enhanced therapy
Active Comparator: Standard therapy Benzathine penicillin G intramuscular 2.4 million units A single intramuscular injection of 2.4 million units of benzathine penicillin G	Drug: Benzathine penicillin G intramuscular 2.4 million units; A single dose of intramuscular 2.4 million units of benzathine penicillin G; Other Names: Standard therapy

Outcome Measures

Primary Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosed with HIV by ELISA and confirmed by Western blot

• Positive Rapid Plasma Reagin and treponema pallidum particle agglutination tests

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Baylor College of Medicine

Investigators

• Principal Investigator: Jose A Serpa-Alvarez, MD, Assistant Professor (Medicine: Infectious Disease)

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jose Serpa-Alvarez, Co-Investigator, Baylor College of Medicine
• ClinicalTrials.gov Identifier: NCT02611765
• Other Study ID Numbers: H-22816
• First Posted: Nov 23, 2015
• Last Update Posted: May 17, 2016
• Last Verified: Apr 1, 2016

• Additional relevant MeSH terms: Syphilis; Penicillins; Penicillin G; Penicillin G Benzathine; Penicillin G Procaine

Study Results

Participant Flow

Arm/Group Title	Enhanced Therapy	Standard Therapy
Arm/Group Description	Three doses of 2.4 million units of intramuscular benzathine penicillin G administered weekly (a total of 7.2 million units) Enhanced therapy: Three doses of intramuscular 2.4 million units of benzathine penicillin G administered weekly (a total of 7.2 million units).	A single intramuscular injection of 2.4 million units of benzathine penicillin G Standard therapy: A single dose of intramuscular 2.4 million units of benzathine penicillin G
Period Title: Overall Study
STARTED	29	35
COMPLETED	27	29
NOT COMPLETED	2	6

Baseline Characteristics

Arm/Group Title	Enhanced Therapy	Standard Therapy	Total
Arm/Group Description	Three doses of 2.4 million units of intramuscular benzathine penicillin G administered weekly (a total of 7.2 million units) Enhanced therapy: Three doses of intramuscular 2.4 million units of benzathine penicillin G administered weekly (a total of 7.2 million units).	A single intramuscular injection of 2.4 million units of benzathine penicillin G Standard therapy: A single dose of intramuscular 2.4 million units of benzathine penicillin G	Total of all reporting groups
Overall Participants	29	35	64
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35 (11)	35 (10)	35 (10)
Sex: Female, Male (Count of Participants)
Female	2 6.9%	1 2.9%	3 4.7%
Male	27 93.1%	34 97.1%	61 95.3%
Race/Ethnicity, Customized (participants) [Number]
Whites	1 3.4%	6 17.1%	7 10.9%
African Americans	15 51.7%	22 62.9%	37 57.8%
Hispanics	13 44.8%	7 20%	20 31.3%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Enhanced Therapy	Standard Therapy
Arm/Group Description	Three doses of 2.4 million units of intramuscular benzathine penicillin G administered weekly (a total of 7.2 million units) Enhanced therapy: Three doses of intramuscular 2.4 million units of benzathine penicillin G administered weekly (a total of 7.2 million units).	A single intramuscular injection of 2.4 million units of benzathine penicillin G Standard therapy: A single dose of intramuscular 2.4 million units of benzathine penicillin G
Measure Participants	29	35
Number [participants]	27 93.1%	28 80%

Adverse Events

Arm/Group Title	Enhanced Therapy		Standard Therapy
Arm/Group Description	Three doses of 2.4 million units of intramuscular benzathine penicillin G administered weekly (a total of 7.2 million units) Enhanced therapy: Three doses of intramuscular 2.4 million units of benzathine penicillin G administered weekly (a total of 7.2 million units).		A single intramuscular injection of 2.4 million units of benzathine penicillin G Standard therapy: A single dose of intramuscular 2.4 million units of benzathine penicillin G
All Cause Mortality
	Enhanced Therapy		Standard Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Enhanced Therapy		Standard Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/29 (0%)		0/35 (0%)
Other (Not Including Serious) Adverse Events
	Enhanced Therapy		Standard Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/29 (0%)		0/35 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.