Phase II trial evaluating the clinical efficacy of cefixime for treatment of active syphilis in non-pregnant women in Brazil (CeBra)

Melanie M Taylor, Edna Oliveira Kara, Maria Alix Leite Araujo, Mariangela Freitas Silveira, Angelica Espinosa Miranda, Ivo Castelo Branco Coelho, Maria Luiza Bazzo, Gerson Fernando Mendes Pereira, Silvana Pereira Giozza, Ximena Pamela Díaz Bermudez, Maeve B Mello, Ndema Habib, My Huong Nguyen, Soe Soe Thwin, Nathalie Broutet, Melanie M Taylor, Edna Oliveira Kara, Maria Alix Leite Araujo, Mariangela Freitas Silveira, Angelica Espinosa Miranda, Ivo Castelo Branco Coelho, Maria Luiza Bazzo, Gerson Fernando Mendes Pereira, Silvana Pereira Giozza, Ximena Pamela Díaz Bermudez, Maeve B Mello, Ndema Habib, My Huong Nguyen, Soe Soe Thwin, Nathalie Broutet

Abstract

Background: Syphilis is a sexually and vertically transmitted infection caused by the bacteria Treponema pallidum for which there are few proven alternatives to penicillin for treatment. For pregnant women infected with syphilis, penicillin is the only WHO-recommended treatment that will treat the mother and cross the placenta to treat the unborn infant and prevent congenital syphilis. Recent shortages, national level stockouts as well as other barriers to penicillin use call for the urgent identification of alternative therapies to treat pregnant women infected with syphilis.

Methods: This prospective, randomized, non-comparative trial will enroll non-pregnant women aged 18 years and older with active syphilis, defined as a positive rapid treponemal and a positive non-treponemal RPR test with titer ≥1:16. Women will be a, domized in a 2:1 ratio to receive the oral third generation cephalosporin cefixime at a dose of 400 mg two times per day for 10 days (n = 140) or benzathine penicillin G 2.4 million units intramuscularly based on the stage of syphilis infection (n = 70). RPR titers will be collected at enrolment, and at three, six, and nine months following treatment. Participants experiencing a 4-fold (2 titer) decline by 6 months will be considered as having an adequate or curative treatment response.

Discussion: Demonstration of efficacy of cefixime in the treatment of active syphilis in this Phase 2 trial among non-pregnant women will inform a proposed randomized controlled trial to evaluate cefixime as an alternative treatment for pregnant women with active syphilis to evaluate prevention of congenital syphilis.

Trial registration: Trial identifier: www.Clinicaltrials.gov, NCT03752112. Registration Date: November 22, 2018.

Keywords: Alternative treatment; Benzathine penicillin; Congenital syphilis; Sexually transmitted infections; Syphilis; cefixime.

Conflict of interest statement

The principal investigators and co-authors have declared that no competing interests exist.

Figures

Fig. 1
Fig. 1
Standard care for syphilis diagnosis and treatment as per the Brazil Ministry of Health guidelines [34]. *NTT: Non treponemal test such as VDRL or RPR

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