Penicillin Therapeutic Drug Monitoring in the Treatment of Infectious Syphilis. Do Low Serum Penicillin Levels Correlate With Treatment Failure? - Full Text View

Purpose

Syphilis is a sexually transmitted infection that causes genital sores and rash, but in some circumstances may result in more severe and unexpected symptoms. These severe symptoms could include eye infections, meningitis (infection of the membranes covering the brain and spinal cord), and liver infection. If not properly treated, syphilis can also lead to heart problems and dementia (a decline in reasoning, memory and other mental abilities) years down the road. There has been an increase in the number of reported cases of syphilis in North America, Europe, and Australia over the past decade. The number of new syphilis infections in Canada has increased roughly 10-fold over the past 10 years.

Since 1943, the antibiotic penicillin has been used to treat syphilis; however, very little information has been gathered to determine the proper dose of penicillin or appropriate duration of treatment. Added to this, several studies have shown that the recommended dose of penicillin fails to cure syphilis in 20-30% of patients. Since the number of people infected with syphilis is increasing, and since syphilis has the potential to cause serious disease, the investigators need better information on how to treat syphilis effectively.

This study aims to determine whether the current dose of penicillin recommended to treat syphilis is sufficient to cure the infection. Specifically the investigators will try to determine whether the amount of penicillin in your blood 3 and 7 days after receiving treatment for syphilis is sufficient to cure the infection as demonstrated by a blood test 6 or 12 months from now. This study is a multi-centered trial based in Ottawa but with centers recruiting both in Montreal and Toronto. A total of 120 participants with syphilis will be recruited into this study. The treatment you will receive for syphilis in this study does not differ from that you would receive normally; the investigators are only observing the levels of penicillin in your blood and relating them with the outcome of treatment.

Condition	Intervention
Syphilis Primary Syphilis Secondary Syphilis Early-Latent Syphilis	Drug: Regular Treatment for Syphilis

Study Type:	Observational
Study Design:	Observational Model: Cohort Time Perspective: Prospective
Official Title:	Penicillin Therapeutic Drug Monitoring in the Treatment of Infectious Syphilis. Do Low Serum Penicillin Levels Correlate With Treatment Failure?

Resource links provided by NLM:

MedlinePlus related topics: Syphilis

U.S. FDA Resources

Further study details as provided by Ottawa Hospital Research Institute:

Primary Outcome Measures:

Penicillin and Treatment Failure [ Time Frame: 6 months post-treatment ] [ Designated as safety issue: No ]
To determine if serum penicillin concentrations measured at days 3 and 7 post-treatment differ between those who achieve successful treatment of infectious syphilis versus those who experience treatment failure.

Secondary Outcome Measures:

HIV and Treatment Failure [ Time Frame: 6 months post-treatment ] [ Designated as safety issue: No ]
To determine if serum penicillin levels and treatment failures differ between HIV-positive and HIV-negative individuals.

Estimated Enrollment:	120
Study Start Date:	September 2011

Groups/Cohorts	Assigned Interventions
Syphilis Patients Individuals presenting for treatment of primary, secondary or early latent syphilis at the Ottawa Hospital Immunodeficiency Clinic, the Ottawa Sexual Health Clinic or its satellite GayZone, the Montreal Chest Institute Immunodeficiency Clinic, or the Toronto General Immunodeficiency Clinic will be invited by their attending health care worker to participate in this study. Only patients presenting for and requiring treatment of infectious syphilis will be asked to participate.	Drug: Regular Treatment for Syphilis Drug: Benzathine Penicillin G (Bicillin) Dose: 2.4 million units Mode of Administration: intramuscular injection Duration of Treatment: one dose Health Canada approved indication: Yes

Groups/Cohorts

Assigned Interventions

Syphilis Patients

Individuals presenting for treatment of primary, secondary or early latent syphilis at the Ottawa Hospital Immunodeficiency Clinic, the Ottawa Sexual Health Clinic or its satellite GayZone, the Montreal Chest Institute Immunodeficiency Clinic, or the Toronto General Immunodeficiency Clinic will be invited by their attending health care worker to participate in this study. Only patients presenting for and requiring treatment of infectious syphilis will be asked to participate.

Drug: Regular Treatment for Syphilis

Drug: Benzathine Penicillin G (Bicillin)

Dose: 2.4 million units

Mode of Administration: intramuscular injection

Duration of Treatment: one dose

Health Canada approved indication: Yes

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

Individuals presenting for treatment of primary, secondary or early latent syphilis will be invited by their attending health care worker to participate in this study. Only patients presenting for and requiring treatment of infectious syphilis will be asked to participate.

Criteria

Inclusion Criteria:

Participants must meet all of the following criteria to be considered eligible for entry into the study:

At least 18 years of age
Presenting with clinical signs of either primary or secondary syphilis; or with early latent syphilis and documented negative serology within the past 12 months.
Positive syphilis serology (reactive CMIA and TP-PA) with a defined RPR titer at the time of diagnosis and enrolment
Able to provide informed consent
Able to communicate in either English of French
Able to return for follow-up

Exclusion Criteria:

Participants are not eligible to participate in the study if any of the following conditions are met:

Diagnosis of late latent syphilis, tertiary syphilis, or syphilis of unknown duration
Allergy to penicillin
Diagnosis of neurosyphilis requiring treatment with intravenous penicillin
Treatment with doxycycline or ceftriaxone
Treatment with more than one intramuscular dose of benzathine penicillin G
Treatment with any antibiotics within the 6 weeks prior to enrolment
Pregnant or breastfeeding
Any immune modulating therapy
Patient is unable or unwilling to return for blood sampling at 3 and 7 days post treatment

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01540227

Locations

Canada, Ontario
The Ottawa Hospital
Ottawa, Ontario, Canada, K1H 8L6
Ottawa Sexual Health Clinic/GayZone
Ottawa, Ontario, Canada, K1N 5P7
Toronto General Hospital
Toronto, Ontario, Canada, M5G 2C4

Sponsors and Collaborators

Ottawa Hospital Research Institute

CIHR Canadian HIV Trials Network

Investigators

Principal Investigator:

Paul A MacPherson, MD/PhD

The Ottawa Hospital/The University of Ottawa/OHRI

More Information

No publications provided

Responsible Party:	Paul MacPherson, Physician/Scientist, Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier:	NCT01540227 History of Changes
Other Study ID Numbers:	CTN PT-011
Study First Received:	February 16, 2012
Last Updated:	April 18, 2012
Health Authority:	Canada: Health Canada

Keywords provided by Ottawa Hospital Research Institute:

Syphilis
Penicillin

Additional relevant MeSH terms:

Chancre
Syphilis
Syphilis, Latent
Treponemal Infections
Gram-Negative Bacterial Infections
Bacterial Infections

Spirochaetales Infections
Sexually Transmitted Diseases, Bacterial
Sexually Transmitted Diseases
Infection
Genital Diseases, Male
Genital Diseases, Female

ClinicalTrials.gov processed this record on June 13, 2013