Cefixime for Alternative Syphilis Treatment

Clinical Trial Evaluating the Clinical Efficacy of Cefixime for Treatment of Early Syphilis

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.

Study Overview

• Status: Completed
• Conditions: Syphilis; Early Syphilis
• Intervention / Treatment: Drug: Benzathine Penicillin G; Drug: Cefixime 400 milligram Oral Capsule [Suprax]

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.

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Beverly Hills, California, United States, 90211
      • AHF Westside
    • Los Angeles, California, United States, 90015
      • AHF Downtown Healthcare Center
    • Los Angeles, California, United States, 90018
      • AHF Carl Bean
    • Los Angeles, California, United States, 90027
      • AHF Hollywood Healthcare Center
    • Los Angeles, California, United States, 90027
      • AHF Wellness on Western Center
    • Oakland, California, United States, 94606
      • AHF Oakland Wellness Center
    • Oakland, California, United States, 94609
      • AHF Healthcare Center Oakland
    • San Francisco, California, United States, 94114
      • AHF San Francisco
    • Sherman Oaks, California, United States, 91403
      • AHF Valley
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • AHF Las Vegas Healthcare Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 18 years of age or older and able to provide informed consent
2. Cases of primary, secondary or early latent syphilis with RPR titer ≥1:8 within 3 weeks prior to enrollment.
3. 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
4. Non-cephalosporin allergic
5. 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
6. Able to swallow pills

Exclusion Criteria:

1. Pregnancy or positive pregnancy test
2. Serofast RPR titer (prior titer 1:8 or greater)
3. Recent (less than 7 days) or concomitant antimicrobial therapy with activity against syphilis.
4. Cephalosporin allergy: previous episode of flushing, urticaria, angioedema, rhinitis, bronchospasm, and anaphylactic shock, rash after taking cephalosporin.
5. Penicillin allergy: previous episode of flushing, urticaria, angioedema, rhinitis, bronchospasm, and anaphylactic shock, rash after receiving Penicillin.
6. Has a medical condition or other factor that might affect their ability to follow the protocol

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Benzathine Penicillin G; 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; 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
Experimental: Cefixime Group; 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]; The intervention group will receive Cefixime 400mg, one tablet twice per day, for ten consecutive days; 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

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Collaborators: AIDS Healthcare Foundation
• Investigators: Principal Investigator: Jeffrey D Klausner, MD MPH, University of California, Los Angeles; Principal Investigator: David Tellalian, MD, AIDS Helthcare Foundation

Publications and helpful links

General Publications

• Mehta SN, Stafylis C, Tellalian DM, Burian PL, Okada CM, Millner CE, Mejia CM, Klausner JD. Clinical trial protocol to evaluate the efficacy of cefixime in the treatment of early syphilis. Trials. 2020 Dec 9;21(1):1009. doi: 10.1186/s13063-020-04885-z.

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2018
• Primary Completion (Actual): January 30, 2021
• Study Completion (Actual): January 30, 2021

Study Registration Dates

• First Submitted: September 4, 2018
• First Submitted That Met QC Criteria: September 4, 2018
• First Posted (Actual): September 6, 2018

Study Record Updates

• Last Update Posted (Actual): July 26, 2022
• Last Update Submitted That Met QC Criteria: July 5, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: syphilis; penicillin; cefixime
• Additional Relevant MeSH Terms: Infections; Communicable Diseases; Sexually Transmitted Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Sexually Transmitted Diseases, Bacterial; Spirochaetales Infections; Treponemal Infections; Syphilis; Anti-Infective Agents; Anti-Bacterial Agents; Penicillins; Penicillin G Benzathine; Penicillin G; Penicillin G Procaine; Cefixime
• Other Study ID Numbers: 18-000665; 20181796 (Other Identifier: Western IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Due to the sensitive nature of the data, participant data will not be provided or shared with other researchers, apart from the members of the research team or regulatory authorities

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No