Cefixime Versus Benzathine Penicillin G in Treatment of Early Syphilis

Cefixime Versus Benzathine Penicillin G in Treatment of Early Syphilis - a Randomized, Multicentre, Non-inferiority, Open Label Trial

This study evaluates the efficacy (non-inferiority) and safety of a new antibiotic treatment (cefixime), which has been previously used for single dose therapy of gonorrhoea in many years , in the treatment of early syphilis. Participants will be randomized to one of two study arms and will receive either expirimental regimen (cefixime) or the current standard antibiotic regimen (benzathine penicillin G). New treatment alternatives for syphilis could ensure that people are appropriately treated during periods or in settings of benzathine penicillin G stock out, penicillin allergy, or other intolerance to penicillin injection. This study may also identify an oral regimen for settings in which injections are not feasible.

Study Overview

• Status: Terminated
• Conditions: Syphilis
• Intervention / Treatment: Drug: Cefixime 400mg; Drug: Benzathine penicillin 2.4 million units

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 4

Contacts and Locations

Study Locations

• Czech Republic
  • Prague, Czech Republic, 18081
    • Fakultni nemocnice Bulovka
  • Praha, Czech Republic, 10000
    • Národní referenční laboratoř pro syfilis, Státní zdravotní ústav

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 18 years of age or older
2. Non-pregnant, non breastfeeding
3. Able to provide informed consent
4. Clinically or laboratory-confirmed primary, secondary or early latent syphilis with a positive rapid treponemal test and an RPR/VDRL titer equal to or greater than 1:8
5. Non-cephalosporin allergic
6. Non-penicillin allergic
7. Agree to be occasionally called by study staff to be reminded to take study drug
8. Willing to attend follow-up visits

Exclusion Criteria:

1. Under 18 years of age
2. Pregnancy, breastfeeding
3. Prior history of syphilis in last two years
4. Allergy or contraindication to penicillin or cephalosporins (including allergy to cefixime)
5. Systemic antibiotic therapy in last two weeks
6. Previous enrollment in the study
7. Presenting a situation or condition that would not allow reliable study follow up (For example: frequent travel, alcohol abuse or substance misuse)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cefixime; cefixime 400 mg taken orally two times a day for 14 consecutive days	Drug: Cefixime 400mg; cefixime 400 mg taken orally two times a day for 14 consecutive days
Active Comparator: benzathine penicillin G; benzathine penicillin G 2.4 MIU single dose intramuscularly	Drug: Benzathine penicillin 2.4 million units; single dose of benzathine penicillin G 2.4 MIU intramuscularly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serological cure	a 4-fold or more (≥2 dilution steps) decrease in rapid plasma reagin (RPR) or veneral disease reach laboratory test (VDRL) titer	from baseline (treatment) to 3 months after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary serological cure	a 4-fold or more (≥2 dilution steps) decrease in rapid plasma reagin (RPR) or veneral disease reach laboratory test (VDRL) titer	from baseline (treatment) to 6 and 12 months after treatment
Treatment safety	Occurrence of treatment-related severe adverse events in treatment groups	from baseline till the end of follow-up (12 months from baseline)

Collaborators and Investigators

• Sponsor: Bulovka Hospital
• Collaborators: Örebro University, Sweden; Všeobecná fakultní nemocnice Praha; Národní referenční laboratoř pro syfilis, Státní zdravotní ústav

Study record dates

Study Major Dates

• Study Start (Actual): July 13, 2021
• Primary Completion (Actual): August 1, 2024
• Study Completion (Actual): August 1, 2024

Study Registration Dates

• First Submitted: March 26, 2025
• First Submitted That Met QC Criteria: March 26, 2025
• First Posted (Actual): April 2, 2025

Study Record Updates

• Last Update Posted (Actual): April 2, 2025
• Last Update Submitted That Met QC Criteria: March 26, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: treatment; syphilis; cefixime
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Infections; Communicable Diseases; Sexually Transmitted Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Negative Bacterial Infections; Spirochaetales Infections; Sexually Transmitted Diseases, Bacterial; Treponemal Infections; Syphilis; Third Generation Cephalosporins; Beta Lactam Antibiotics; Anti-Bacterial Agents; Anti-Infective Agents; Penicillins; Cefixime; Penicillin G; Penicillin G Benzathine; Penicillin G Procaine
• Other Study ID Numbers: 1.6.2021/10071/EK-Z

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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