Clinical trial NCT03660488: Cefixime for Alternative Syphilis Treatment
Official title: Clinical Trial Evaluating the Clinical Efficacy of Cefixime for Treatment of Early Syphilis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Syphilis
Early Syphilis
Keywords: syphilis
cefixime
penicillin
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
Collaborators: name: AIDS Healthcare Foundation
First posted: 2018-09-06
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Treatment Response
timeFrame: 3 or 6 months after treatment completion
Secondary outcomes:
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: AHF Westside
state: California
city: Los Angeles
country: United States
facility: AHF Downtown Healthcare Center
state: California
city: Los Angeles
country: United States
facility: AHF Carl Bean
state: California
city: Los Angeles
country: United States
facility: AHF Hollywood Healthcare Center
state: California
city: Los Angeles
country: United States
facility: AHF Wellness on Western Center
state: California
city: Oakland
country: United States
facility: AHF Oakland Wellness Center
state: California
city: Oakland
country: United States
facility: AHF Healthcare Center Oakland
state: California
city: San Francisco
country: United States
facility: AHF San Francisco
state: California
city: Sherman Oaks
country: United States
facility: AHF Valley
state: California
city: Las Vegas
country: United States
facility: AHF Las Vegas Healthcare Center
state: Nevada
Study officials:
affiliation: University of California, Los Angeles
name: Jeffrey D Klausner, MD MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: AIDS Helthcare Foundation
name: David Tellalian, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.