Cefixime for Alternative Syphilis Treatment

Study Overview
=================
Brief Summary
-----------------
The goal of the study is to evaluate the efficacy of oral cefixime as an alternative treatment for syphilis infection. One hundred adult patients (≥18 years old) with syphilis infection (positive Treponema Pallidum Particle Agglutination assay and RPR titer ≥ 1/8) will be recruited. Participants will be randomized (1:1) to receive either the standard of care Penicillin or Cefixime. During the study, participants will visit the clinic up to 5 times; at baseline visit, at 3, 6, 12 months after treatment initiation. Participants of the cefixime group will be required to visit the clinic 14 days after treatment initiation. In each visit, participants will be asked about current symptoms and do laboratory tests for syphilis (RPR). Subjects who have a 4-fold decrease (from study entry RPR) in RPR titers from baseline at 6 months will be considered a positive treatment response.

Detailed Description
-----------------
Syphilis is a major issue worldwide causing 5.6 million new cases of syphilis worldwide, of which over 900,000 are pregnant women. It is also responsible for congenital infections causing fetal loss or stillbirth or, in a live-born infant, neonatal death, prematurity and low birth weight. Penicillin is the currently used treatment. However, lack of penicillin and alternatives to treatment often hinder treatment and prevention efforts. Cefixime is an FDA-approved, orally administered third-generation cephalosporin that is currently used for the treatment of a wide range of infections, including urinary tract infections. Our goal is to evaluate the efficacy and safety of oral cefixime as an alternative treatment for syphilis infection. One hundred adult patients (≥18 years old) with syphilis infection will be recruited. Eligible participants will have laboratory-confirmed syphilis infection with a positive Treponema pallidum Particle Agglutination (TPPA) assay and RPR (Rapid Plasma Reagin ) titer ≥ 1/8. Participants will be randomized (1:1) to receive either the standard of care Penicillin or Cefixime. During the study, participants will visit the clinic 5 times; at baseline visit, demographic, clinical information and laboratory test results for syphilis will be recorded and treatment will start. Depending on the study group, the treatment plan will be oral Cefixime 400mg, twice per day for ten consecutive days or one dose of intramuscular Penicillin. Patients will be required to visit the clinic two weeks after treatment initiation to verify adverse effects. Follow up visits will occur at 3, 6 and 12 months after treatment initiation. In each visit, participants will be asked about current symptoms, interval sexual history, concomitant antibiotic use and possible adverse reactions. Subjects will also have a venipuncture blood specimen collected for syphilis testing (RPR). Subjects who have a 4-fold decrease (from study entry RPR) in RPR titers from baseline at 6 months will be considered a positive treatment response.

Official Title
-----------------
Clinical Trial Evaluating the Clinical Efficacy of Cefixime for Treatment of Early Syphilis

Conditions
-----------------
Syphilis, Early Syphilis

Intervention / Treatment
-----------------
* Drug: Cefixime 400 milligram Oral Capsule [Suprax]
* Drug: Benzathine Penicillin G


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18 years of age or older and able to provide informed consent Cases of primary, secondary or early latent syphilis with RPR titer ≥1:8 within 3 weeks prior to enrollment. HIV infected individuals willing to participate in the study must have CD4 count ≥350 cells/μl within the last 4 weeks and be virally suppressed (i.e., viral load ≤ 200 copies/mL) for HIV for the 6 months prior to enrolment with the most recent results within the last 4 weeks. inclusion Non-cephalosporin allergic Able to travel to the clinic once a day or be available for phone calls or receive text messages for at least 7-10 days and willing to attend follow-up visits Able to swallow pills Exclusion Criteria: Pregnancy or positive pregnancy test Serofast RPR titer (prior titer 1:8 or greater) Recent (less than 7 days) or concomitant antimicrobial therapy with activity against syphilis. Cephalosporin allergy: previous episode of flushing, urticaria, angioedema, rhinitis, bronchospasm, and anaphylactic shock, rash after taking cephalosporin. Penicillin allergy: previous episode of flushing, urticaria, angioedema, rhinitis, bronchospasm, and anaphylactic shock, rash after receiving Penicillin. Has a medical condition or other factor that might affect their ability to follow the protocol

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Benzathine Penicillin G<br>Patients of the Penicillin Group will receive the standard of care treatment. This is one intramuscular injection of 2.4 million units Benzathine Penicillin G. The group will consist of 50 patients. | Drug: Benzathine Penicillin G<br>* The control group will receive Benzathine Penicillin G 2.4 Million Units intramuscularly for treatment of syphilis. Penicillin is the indicated treatment for syphilis infection<br>|
| Experimental: Cefixime Group<br>Patients of the Cefixime Group will receive Cefixime 400 mg, per os, one tablet, two times per day, for ten consecutive days. The study team will provide the medication. The group will consist of 50 patients. | Drug: Cefixime 400 milligram Oral Capsule [Suprax]<br>* The intervention group will receive Cefixime 400mg, one tablet twice per day, for ten consecutive days<br>* Other names: Suprax;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Response | subjects who have a 4-fold decrease (from study entry Rapid plasma reagin) in Rapid plasma reagintiters from baseline at 3 or 6 months will be considered a positive treatment response. | 3 or 6 months after treatment completion | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
syphilis, cefixime, penicillin