Cefixime vs. Penicillin for Syphilis

Overseen By Jeffrey D Klausner

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Southern California

Must be taking: HIV treatment

Must not be taking: Azithromycin, Doxycycline, Ceftriaxone, others

Disqualifiers: Pregnancy, Neurosyphilis, Allergy to penicillin, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 10 days

400 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two antibiotics, cefixime taken by mouth and benzathine penicillin G given as an injection, to treat early syphilis. It includes patients with and without HIV to find an effective alternative to penicillin. The study aims to help those who are allergic to penicillin or affected by penicillin shortages. Cefixime is being tested as an alternative to penicillin for treating early syphilis, especially for those allergic to penicillin or during penicillin shortages.

Will I have to stop taking my current medications?

The trial requires that you have not taken certain antibiotics like azithromycin, doxycycline, ceftriaxone, or other beta-lactam antibiotics (like amoxicillin) in the past 7 days. If you are on HIV treatment, you must continue it and be virologically suppressed.

Is cefixime generally safe for human use?

Cefixime has been tested in various clinical trials for different infections, and while it is generally effective, some people have experienced mild side effects like skin rashes and stomach discomfort. These side effects usually go away after stopping the medication. ^{1 2 3 4 5}

How does the drug Cefixime differ from other treatments for syphilis?

Cefixime is an oral antibiotic that offers a convenient alternative to the standard injectable treatment for syphilis, Benzathine Penicillin G. While traditionally used for urinary and respiratory infections, its oral administration could make it more accessible for patients who prefer or require non-injection options. ^{1 2 3 5 6}

What data supports the effectiveness of the drug Cefixime for treating infections?

Cefixime has shown high effectiveness in treating various infections, such as urinary tract infections and respiratory tract infections, with clinical success rates ranging from 76% to 94% in different studies. It was also effective in treating typhoid fever in children, with a cure rate of 93.3%. ^{1 2 3 5 7}

Who Is on the Research Team?

Jeffrey D Klausner, MD

Principal Investigator

University of Southern California

Are You a Good Fit for This Trial?

This trial is for adults diagnosed with primary, secondary, or early latent syphilis who have an RPR titer of at least 1:8. People with HIV can join if they're on treatment and either have a low viral load or a CD4 count over 350. You can't join if you're pregnant, show signs of neurosyphilis, recently took certain antibiotics, are allergic to cephalosporins/penicillin, or can't make follow-up visits.

Inclusion Criteria

I have been diagnosed with syphilis and my recent test shows a high level of infection.

I have HIV, am on treatment, and my viral load is under control or my CD4 count is above 350.

Able to provide informed consent

Exclusion Criteria

Self-reported allergy to cephalosporins or penicillin

Individuals with HIV infection who report HIV treatment interruption for more than 4 weeks since their most recent viral load or CD4 test

I am showing signs of a brain or nerve condition caused by syphilis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either cefixime (400mg orally, twice a day, for 10 days) or a single intramuscular injection of benzathine penicillin G

10 days

Follow-up

Participants are monitored for clinical outcomes and serological response (RPR titer) every 3 months for 9 months

9 months

3 visits (in-person) every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Benzathine Penicillin G
• Cefixime

Trial Overview The study compares the effectiveness of two treatments for syphilis: Cefixime (400mg) versus benzathine penicillin G. It aims to determine which medication works better in curing the infection.

How Is the Trial Designed?

Group I: Cefixime Experimental Treatment 1 Intervention

Oral cefixime 400mg, taken twice a day for 10 days

Group II: Benzathine Penicillin G Active Control 1 Intervention

Single intramuscular injection of 2.4 million units of benzathine penicillin G

Who Is Running the Clinical Trial?

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

AIDS Healthcare Foundation

Collaborator

Trials

19

Recruited

147,000+

Universidad Peruana Cayetano Heredia

Collaborator

Trials

80

Recruited

62,300+

Published Research Related to This Trial

Cefixime was tested in multicenter trials involving 406 patients (137 children and 269 adults) with respiratory and urinary tract infections, showing positive clinical and bacteriological outcomes in 76-90% of cases.

The medication had a low incidence of adverse reactions, such as skin eruptions and dyspepsia, which were rare and did not necessitate specific treatment, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical efficacy of cefixime (results of multicenter trials)]. Sereda, EV., Gusel', VA., Feshchenko, IuI., et al.[2016]

Cefixime (CFIX) demonstrated a high overall clinical effectiveness rate of 98% in treating acute uncomplicated cystitis among 92 female patients, while showing a 57% effectiveness rate in complicated urinary tract infections (UTIs) among 42 patients.

The safety profile of CFIX was favorable, with only 1.7% of patients experiencing subjective adverse reactions, and any abnormal laboratory findings resolved after stopping the medication, indicating it is a clinically useful oral antibiotic for UTIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical evaluation of cefixime (CFIX) in the treatment of urinary tract infection]. Sonoda, T., Matsuda, M., Nakano, E., et al.[2013]

Cefixime (CFIX) demonstrated high therapeutic effectiveness in treating urinary tract infections, achieving a 100% clinical efficacy rate in women with acute uncomplicated cystitis and a 63% efficacy rate in patients with complicated UTIs, based on a study of 129 cases.

The treatment was generally safe, with only 3.1% of patients experiencing mild adverse reactions, all of which resolved after stopping the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical experience with cefixime in urinary tract infections]. Kameoka, H., Takano, Y., Miyoshi, S., et al.[2016]

Cefixime demonstrated a high clinical success rate of 94% in treating community-acquired acute lower respiratory tract infections, which is comparable to other antibiotics, with eradication rates reaching 92%.

The safety profile of cefixime was similar to that of other antibiotics, with adverse experiences reported in 34% to 50% of patients across treatment groups, primarily mild to moderate gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cefixime in the treatment of patients with lower respiratory tract infections: results of US clinical trials. Quintiliani, R.[2019]

In a trial involving 40 children with culture-positive typhoid fever, cefixime demonstrated a significantly higher clinical cure rate of 90% compared to 45% for chloramphenicol after 14 days of treatment.

Cefixime proved to be highly effective, curing 93.3% of all cases when including patients who switched from chloramphenicol to cefixime, highlighting its potential as a preferred treatment option for typhoid fever in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparative study of cefixime and chloramphenicol in children with typhoid fever. Rabbani, MW., Iqbal, I., Malik, MS.[2013]

Cefixime (CFIX) was highly effective in treating acute uncomplicated cystitis, with an overall clinical efficacy of 80.8% in a study of 94 patients, and it successfully eradicated 97.9% of the bacterial strains isolated from patients.

The treatment was well-tolerated, with only one patient (0.7%) reporting mild side effects, and no significant drug-related laboratory abnormalities were observed, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical evaluation of cefixime in the treatment of acute uncomplicated cystitis]. Togashi, M., Kubota, M., Nagamori, S., et al.[2013]

SY5555, a new oral penem antibiotic, demonstrated superior antibacterial activity against several common bacteria, including methicillin-susceptible Staphylococcus aureus and Streptococcus pneumoniae, compared to cefaclor, cefixime, and cefteram.

Unlike many beta-lactam antibiotics, SY5555 was not hydrolyzed by various beta-lactamases, suggesting it may have a more targeted action against certain bacterial strains, although it was still susceptible to specific beta-lactamases from Xanthomonas maltophilia and Pseudomonas aeruginosa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro antibacterial activity and beta-lactamase stability of SY5555, a new oral penem antibiotic. Inoue, E., Mitsuhashi, S.[2021]

Citations

1. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Clinical efficacy of cefixime (results of multicenter trials)]. [2016]

2. Japan pubmed.ncbi.nlm.nih.gov

[Clinical evaluation of cefixime (CFIX) in the treatment of urinary tract infection]. [2013]

3. Japan pubmed.ncbi.nlm.nih.gov

[Clinical experience with cefixime in urinary tract infections]. [2016]

4. United States pubmed.ncbi.nlm.nih.gov

Cefixime in the treatment of patients with lower respiratory tract infections: results of US clinical trials. [2019]

5. Pakistan pubmed.ncbi.nlm.nih.gov

A comparative study of cefixime and chloramphenicol in children with typhoid fever. [2013]

6. Japan pubmed.ncbi.nlm.nih.gov

[Clinical evaluation of cefixime in the treatment of acute uncomplicated cystitis]. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

In vitro antibacterial activity and beta-lactamase stability of SY5555, a new oral penem antibiotic. [2021]