Cefixime for Alternative Syphilis Treatment

• ClinicalTrials.gov Identifier: NCT03660488
• Recruitment Status: Recruiting
• First Posted: September 6, 2018
• Last Update Posted: May 8, 2020
• Sponsor: University of California, Los Angeles
• Collaborator: AIDS Healthcare Foundation
• Information provided by (Responsible Party): Jeffrey D. Klausner, MD, MPH, University of California, Los Angeles

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Syphilis; Early Syphilis	Drug: Cefixime 400 milligram Oral Capsule [Suprax]; Drug: Benzathine Penicillin G	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Clinical Trial Evaluating the Clinical Efficacy of Cefixime for Treatment of Early Syphilis
• Actual Study Start Date: September 3, 2018
• Estimated Primary Completion Date: June 2021
• Estimated Study Completion Date: October 2021

Arms and Interventions

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 Name: Suprax

Outcome Measures

Primary Outcome Measures :

1. Treatment response [ Time Frame: 6 months after treatment completion ]
   subjects who have a 4-fold decrease (from study entry RPR) in RPR titers from baseline at 3 or 6 months will be considered a positive treatment response.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Jeffrey D Klausner, MD MPH; 3107943221; jdklausner@mednet.ucla.edu

Contact: Chrysovalantis Stafylis, MD MPH; cstafylis@mednet.ucla.edu

Locations

United States, California

AHF Westside; Recruiting

Beverly Hills, California, United States, 90211

Contact: Carl Millner, MD

AHF Downtown Healthcare Center; Recruiting

Los Angeles, California, United States, 90015

Contact: David Tellalian, MD david.tellalian@aidshealth.org

AHF Carl Bean; Recruiting

Los Angeles, California, United States, 90018

Contact: David Tellalian, MD

AHF Hollywood Healthcare Center; Recruiting

Los Angeles, California, United States, 90027

Contact: Pam Burian, PA

AHF Wellness on Western Center; Recruiting

Los Angeles, California, United States, 90027

Contact: Cliff Okada, MD

AHF Oakland Wellness Center; Recruiting

Oakland, California, United States, 94606

Contact: Christopher Mejia, MPH

AHF Healthcare Center Oakland; Recruiting

Oakland, California, United States, 94609

Contact: Seth Glassman, MD

AHF San Francisco; Recruiting

San Francisco, California, United States, 94114

Contact: Seth Glassman, MD

AHF Valley; Recruiting

Sherman Oaks, California, United States, 91403

Contact: James Carroll, MD

United States, Nevada

AHF Las Vegas Healthcare Center; Recruiting

Las Vegas, Nevada, United States, 89109

Contact: Warren Magnus, MD

Sponsors and Collaborators

University of California, Los Angeles

AIDS Healthcare Foundation

Investigators

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Jeffrey D. Klausner, MD, MPH, Professor of Medicine & Public Health, University of California, Los Angeles
• ClinicalTrials.gov Identifier: NCT03660488
• Other Study ID Numbers: 18-000665; 20181796 ( Other Identifier: Western IRB )
• First Posted: September 6, 2018
• Last Update Posted: May 8, 2020
• Last Verified: May 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• 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

• 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

Keywords provided by Jeffrey D. Klausner, MD, MPH, University of California, Los Angeles:

syphilis; cefixime; penicillin

Additional relevant MeSH terms:

Syphilis; Treponemal Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Sexually Transmitted Diseases, Bacterial; Spirochaetales Infections; Sexually Transmitted Diseases; Infection; Penicillins; Cefixime; Penicillin G; Penicillin G Benzathine; Penicillin G Procaine; Anti-Bacterial Agents; Anti-Infective Agents