Trial Evaluating the Clinical Efficacy of Cefixime for Treatment of Early Syphilis in Non-pregnant Women

January 29, 2020 updated by: Melanie Taylor, World Health Organization

Hypotheses The antibiotic, Cefixime, for use in non-pregnant women with early syphilis will be efficacious and safe.

Primary Objective The primary objective of the study is to demonstrate the efficacy, as measured by a 4 fold decrease in Rapid Plasma Reagin (RPR) titer from baseline to 6 months after treatment, with Cefixime 400mg taken orally two times a day for 10 consecutive days.

Secondary Objective The secondary objective of the study is to determine the safety, as measured by the number of grade 3 or greater toxicities experienced, using the NIH/NCI toxicity score, during or after treatment with Cefixime 400mg taken orally two times a day for 10 consecutive days.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Hypotheses The antibiotic, Cefixime, for use in non-pregnant women with early syphilis will be efficacious and safe.

Primary Objective The primary objective of the study is to demonstrate the efficacy, as measured by a 4 fold decrease in Rapid Plasma Reagin (RPR) titer from baseline to 6 months after treatment, with Cefixime 400mg taken orally two times a day for 10 consecutive days.

Secondary Objective The secondary objective of the study is to determine the safety, as measured by the number of grade 3 or greater toxicities experienced, using the NIH/NCI toxicity score (10), during or after treatment with Cefixime 400mg taken orally two times a day for 10 consecutive days.

Methods Study design This is a randomized, non-comparative, open-label study assessing the efficacy and safety of cefixime 400mg taken orally two times a day for 10 consecutive days in non-pregnant women with early syphilis infection.

Study population and enrolment sites Numerous regions of Brazil have experienced increases in syphilis diagnoses during the previous 5 years The study sites were chosen from three cities in three separate regions (states) of Brazil based on: (1) increases in syphilis case reports, (2) access to clinics where patients are screened and treated for syphilis; (3) willingness of clinic sites and staff to participate in this research, and (4) the availability of experienced researchers with experience in studying syphilis to serve as co-investigators.

The study population will include non-pregnant women (ages 18 and over) diagnosed with early syphilis (RPR titers >1:8) recruited from 7 clinics in three cities from three states in Brazil. These include: (1) Three clinics in the city of Fortaleza (Ceara State), coordinated by the University of Fortaleza (UNIFOR): (a) Carlos Ribeiro, (a) Meireles, and (c) Federal University. Syphilis epidemiology for each site in Annex 1. (2) Two University ObGyn Clinics in the city of Pelotas (state of Rio Grande do Sul) (5-6 cases of syphilis/week) a) Ambulatorio de Ginecologia e Obstetrícia - Faculdade de Medicina - Universidade Federal de Pelotas and b) Ambulatorio de Ginecologia e Obstetrícia - Campus da Saúde - Universidade Católica de Pelotas; and (3) Two clinics in Vitoria (State of Espirito Santo): (1) Reference Center for Sexually Transmitted Diseases (http://www.vitoria.es.gov.br/cidadao/centro-de-referencia-em-infeccoes-sexualmente-transmissiveis). (2) Hospital Universitário Cassiano Antonio Moraes - UFES.

Patients identified during standard of care testing with a positive rapid syphilis test and an RPR titer of greater than or equal to 1:8 will be referred to the study and offered enrollment according to the following description.

Non-study clinic-site staff will perform the first screening rapid finger-stick test for syphilis. The rapid syphilis test currently used in these clinics detects both new (acute) infection and old treated infection but does not distinguish between the two. Patients that are positive for the syphilis rapid finger-stick test will be notified by non-study staff of this result and the need for additional testing using the RPR test according to standard of care. Blood will be collected for the confirmatory RPR test by non-study staff. These patients will be notified of RPR results in approximately 3 days to 1 week. The results a confirmed syphilis diagnosis and of the RPR test results for those patients that are eligible for enrolment in the study (RPR >1:8) will be provided by a study nurse. The study will be explained to eligible participants (RPR titer of >1:8) by this study nurse, and if women express interest in participating, informed consent will be obtained. It is expected that an enrolment visit could last approximately 1.5 hours.

Patients that are not eligible for the study (negative RPR or RPR with titer <1:8) will receive syphilis RPR results from non-study staff.

Pregnancy tests will be completed on all potential participants and those that test positive will not be enrolled in the study.

The timing of the recruitment process will depend on the number of women diagnosed with syphilis and who have an RPR titer >1:8 and who consent to participate in the study. It is anticipated that enrollment will take approximately 1 year to complete.

To benchmark the performance of benzathine penicillin in the study population being used for cefixime, The investigators will include a contemporary arm of participants that will receive standard of care treatment with benzathine penicillin according to the Brazil national sexually transmitted infection (STI) treatment guidelines. The investigators will use a ratio of 2 patients receiving cefixime to 1 patient receiving benzathine penicillin.

This non-comparator arm of benzathine penicillin will be included to account for study population differences in terms of stage of disease, history of prior infection, experience of re-infection, experience of serofast state, or other co-factors that could impact serological response. An estimate of performance of this standard of care will be calculated, but this will not be compared directly to the study intervention.

The investigators will enrol 180 eligible women into the study: 120 for the cefixime arm and 60 for the benzathine penicillin arm. It is anticipated that enrollment will take approximately 1 year to complete. Patients will be participating in the study for approximately 9 months. The study is expected to last for approximately two years. Women that are referred to the study but decline enrolment will be treated at the clinic following national STI treatment guidelines for syphilis.

Study Type

Interventional

Enrollment (Anticipated)

180

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Melanie M Taylor, MD
  • Phone Number: +41 22 791 2172
  • Email: mtaylor@who.int

Study Contact Backup

  • Name: Edna O Kara, MD
  • Phone Number: +41 22 791 2649
  • Email: karae@who.int

Study Locations

  • Brazil
    • Ceara
      • Fortaleza, Ceara, Brazil
        • Recruiting
        • Fortaleza University
        • Contact:
        • Contact:
        • Principal Investigator:
          • Alix Araujo, PhD
        • Principal Investigator:
          • Mariangela Silveira, MD
        • Principal Investigator:
          • Angelica Miranda, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  1. Female, 18 years of age or older
  2. Non-pregnant
  3. Able to provide informed consent
  4. Test positive for syphilis with a positive TPPA AND an RPR titer equal to or greater than 1:8
  5. Non-cephalosporin allergic
  6. Non-penicillin allergic
  7. Agree to be called once a day by study staff to be reminded to take study drug
  8. Able to swallow pills
  9. Willing to attend follow-up visits at 3, 6, and 9 months after completion of the study treatment
  10. Willing to take oral contraceptive or use condom to prevent pregnancy during the study period
  11. HIV negative

Exclusion Criteria:

1) Female under 18 years of age 2) HIV positive 3) Pregnancy test positive or clinical pregnancy 4) Prior history of syphilis or syphilis treatment within 6 months of study screening 5) Allergy to penicillin or cephalosporins (including allergy to cefixime) 6) In the judgment of the interviewer, has a medical condition or other factor that might affect their ability to follow the protocol 7) Previous enrollment in the study 8) Presenting a condition that would not allow reliable informed consent (alcohol abuse or substance misuse) 9) Lacking mental capacity to give informed consent to participation

-

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cefixime
cefixime 400mg taken orally two times a day for 10 consecutive days in non-pregnant women with early syphilis infection.
Drug: Cefixime
Cefixime 400mg taken orally two times a day for 10 consecutive days in non-pregnant women with early syphilis infection
Other Names:
  • Intervention
Other: Benzathine penicillin
To benchmark the performance of benzathine penicillin in the study population being used for cefixime, the investigators will include a contemporary arm of participants that will receive standard of care treatment with benzathine penicillin according to the Brazil national STI treatment guidelines. The investigators will use a ratio of 2 patients receiving cefixime to 1 patient receiving benzathine penicillin.
Drug: Benzathine penicillin 2.4 million units
Benzathine penicillin 2.4 million units: The investigators will include a contemporary arm of participants that will receive standard of care treatment with Benzathine penicillin 2.4 million units according to the Brazil national STI treatment guidelines. The investigators will use a ratio of 2 patients receiving cefixime to 1 patient receiving benzathine penicillin.This non-comparator arm of benzathine penicillin will be included to account for study population differences in terms of stage of disease, history of prior infection, experience of re-infection, experience of serofast state, or other co-factors that could impact serological response
Other Names:
  • Standard treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quantitative RPR titer change
Time Frame: 6 months following last dose of Cefixime 400 mg
RPR titer response at 6 months
6 months following last dose of Cefixime 400 mg

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE with cefixime
Time Frame: Daily after the first dose of cefixime 400mg orally through 10 days after the first dose
Number of participants with treatment-related adverse events as assessed by CTCAE. Information on side effects will be collected daily for 10 days of administration of cefixime using a pre-established list of most commonly reported side effects and a grade scale will be applied using the Common Terminology Criteria for Adverse Events.
Daily after the first dose of cefixime 400mg orally through 10 days after the first dose
The number of participants reporting tolerability of cefixime
Time Frame: Daily after the first dose of cefixime 400mg orally through 10 days after the first dose and qualitative overall assessment of tolerability measured via questionnaire 14 days after the first dose of cefixime
Tolerability: The number of participants reporting tolerability of cefixime as measured by quantitative reported experience of common side effects and qualitative experience of tolerance of the regimen as collected through daily questionnaires and an end treatment questionnaire at 14 days after the first dose of cefixime.
Daily after the first dose of cefixime 400mg orally through 10 days after the first dose and qualitative overall assessment of tolerability measured via questionnaire 14 days after the first dose of cefixime

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

World Health Organization

Investigators

  • Principal Investigator: Melanie M Taylor, MD, World Health Organization
  • Study Director: Nathalie JN Broutet, MD, World Health Organization
  • Study Chair: Edna O Kara, MD, World Health Organization

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 22, 2019

Primary Completion (Anticipated)

March 30, 2021

Study Completion (Anticipated)

September 30, 2021

Study Registration Dates

First Submitted

November 20, 2018

First Submitted That Met QC Criteria

November 21, 2018

First Posted (Actual)

November 23, 2018

Study Record Updates

Last Update Posted (Actual)

February 5, 2020

Last Update Submitted That Met QC Criteria

January 29, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ERC0003096

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Beginning 9 months and ending 24 months following article publication, the supporting information that will be shared for IPD are all data that underlie the results in the publication.

IPD Sharing Time Frame

Beginning 9 months and ending 24 months following article publication,

IPD Sharing Access Criteria

  • Access will be provided to investigators whose proposed use of data has been approved by an independent review committee identified for this purpose
  • Data whose goal is to achieve aims in the approved proposal
  • The way proposals should be submitted will be decided and informed after WHO standard operating procedure (in development) for this purpose is complete.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Informed Consent Form (ICF)
  • Clinical Study Report (CSR)

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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