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

NCT03752112 | Unknown Phase 1 DMC

• 1 other identifier: ERC0003096
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Syphilis Female

Keywords

Syphilis; Women; Cefixime; Brazil; Sexually Transmitted Infection; STI

Outcome Measures

Primary Outcomes (1)

• Quantitative RPR titer change

  RPR titer response at 6 months

  6 months following last dose of Cefixime 400 mg

Secondary Outcomes (2)

• Number of participants with treatment-related adverse events as assessed by CTCAE with cefixime

  Daily after the first dose of cefixime 400mg orally through 10 days after the first dose

• The number of participants reporting tolerability 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

Study Arms (2)

Cefixime

EXPERIMENTAL

cefixime 400mg taken orally two times a day for 10 consecutive days in non-pregnant women with early syphilis infection.

Drug: Cefixime

Benzathine penicillin

OTHER

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

Interventions

Cefixime DRUG

Cefixime 400mg taken orally two times a day for 10 consecutive days in non-pregnant women with early syphilis infection

Also known as: Intervention

Cefixime

Benzathine penicillin 2.4 million units DRUG

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

Also known as: Standard treatment

Benzathine penicillin

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Participant eligibility is based on biologic gender
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• \) 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

Sponsors & Collaborators

• World Health Organization: lead

Study Sites (1)

Fortaleza University

Fortaleza, Ceará, Brazil

RECRUITING

Related Publications (14)

• Workowski KA, Bolan GA; Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015 Jun 5;64(RR-03):1-137.

  PMID: 26042815 BACKGROUND

• WHO Guidelines for the Treatment of Treponema pallidum (Syphilis). Geneva: World Health Organization; 2016. Available from http://www.ncbi.nlm.nih.gov/books/NBK384904/

  PMID: 27631046 BACKGROUND

• Liang Z, Chen YP, Yang CS, Guo W, Jiang XX, Xu XF, Feng SX, Liu YQ, Jiang G. Meta-analysis of ceftriaxone compared with penicillin for the treatment of syphilis. Int J Antimicrob Agents. 2016 Jan;47(1):6-11. doi: 10.1016/j.ijantimicag.2015.10.020. Epub 2015 Nov 23.

  PMID: 26724187 BACKGROUND

• Norris SJ, Cox DL, Weinstock GM. Biology of Treponema pallidum: correlation of functional activities with genome sequence data. J Mol Microbiol Biotechnol. 2001 Jan;3(1):37-62.

  PMID: 11200228 BACKGROUND

• Faulkner RD, Fernandez P, Lawrence G, Sia LL, Falkowski AJ, Weiss AI, Yacobi A, Silber BM. Absolute bioavailability of cefixime in man. J Clin Pharmacol. 1988 Aug;28(8):700-6. doi: 10.1002/j.1552-4604.1988.tb03203.x.

  PMID: 3216036 BACKGROUND

• Faulkner RD, Bohaychuk W, Haynes JD, Desjardins RE, Yacobi A, Silber BM. The pharmacokinetics of cefixime in the fasted and fed state. Eur J Clin Pharmacol. 1988;34(5):525-8. doi: 10.1007/BF01046715.

  PMID: 3203716 BACKGROUND

• Barbee LA, Nayak SU, Blumer JL, O'Riordan MA, Gray W, Zenilman JM, Golden MR, Griffiss JM. A Phase 1 Pharmacokinetic and Safety Study of Extended-Duration, High-dose Cefixime for Cephalosporin-resistant Neisseria gonorrhoeae in the Pharynx. Sex Transm Dis. 2018 Oct;45(10):677-683. doi: 10.1097/OLQ.0000000000000844.

  PMID: 29624558 BACKGROUND

• Rafal'skii VV, Dovgan' EV, Kozyrev IuV, Gustovarova TA, Khlybova SV, Novoselova AV, Filippenko NG, Likhikh DG. [The efficacy and safety of cefixime and amoxicillin/clavulanate in the treatment of asymptomatic bacteriuria in pregnant women: a randomized, prospective, multicenter study]. Urologiia. 2013 Sep-Oct;(5):24, 26-8. Russian.

  PMID: 24437236 BACKGROUND

• Nurse-Findlay S, Taylor MM, Savage M, Mello MB, Saliyou S, Lavayen M, Seghers F, Campbell ML, Birgirimana F, Ouedraogo L, Newman Owiredu M, Kidula N, Pyne-Mercier L. Shortages of benzathine penicillin for prevention of mother-to-child transmission of syphilis: An evaluation from multi-country surveys and stakeholder interviews. PLoS Med. 2017 Dec 27;14(12):e1002473. doi: 10.1371/journal.pmed.1002473. eCollection 2017 Dec.

  PMID: 29281619 BACKGROUND

• U.S.DEPARTMENT OF HEALTH AND HUMAN SERVICES. National Institutes of Health National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 . https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/Archive/CTCAE_4.0_2009-05-29_QuickReference_8.5x11.pdf

  BACKGROUND

• Hook EW 3rd, Behets F, Van Damme K, Ravelomanana N, Leone P, Sena AC, Martin D, Langley C, McNeil L, Wolff M. A phase III equivalence trial of azithromycin versus benzathine penicillin for treatment of early syphilis. J Infect Dis. 2010 Jun 1;201(11):1729-35. doi: 10.1086/652239.

  PMID: 20402591 BACKGROUND

• Cao Y, Su X, Wang Q, Xue H, Zhu X, Zhang C, Jiang J, Qi S, Gong X, Zhu X, Pan M, Ren H, Hu W, Wei Z, Tian M, Liu W. A Multicenter Study Evaluating Ceftriaxone and Benzathine Penicillin G as Treatment Agents for Early Syphilis in Jiangsu, China. Clin Infect Dis. 2017 Oct 30;65(10):1683-1688. doi: 10.1093/cid/cix611.

  PMID: 29020150 BACKGROUND

• Stafylis C, Keith K, Mehta S, Tellalian D, Burian P, Millner C, Klausner JD. Clinical Efficacy of Cefixime for the Treatment of Early Syphilis. Clin Infect Dis. 2021 Sep 7;73(5):907-910. doi: 10.1093/cid/ciab187.

  PMID: 33640982 DERIVED

• Taylor MM, Kara EO, Araujo MAL, Silveira MF, Miranda AE, Branco Coelho IC, Bazzo ML, Mendes Pereira GF, Pereira Giozza S, Bermudez XPD, Mello MB, Habib N, Nguyen MH, Thwin SS, Broutet N. Phase II trial evaluating the clinical efficacy of cefixime for treatment of active syphilis in non-pregnant women in Brazil (CeBra). BMC Infect Dis. 2020 Jun 10;20(1):405. doi: 10.1186/s12879-020-04980-1.

  PMID: 32522244 DERIVED

MeSH Terms

Conditions

Syphilis; Sexually Transmitted Diseases

Interventions

Cefixime; Methods

Condition Hierarchy (Ancestors)

Treponemal Infections; Spirochaetales Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Sexually Transmitted Diseases, Bacterial; Communicable Diseases; Genital Diseases; Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cefotaxime; Cephacetrile; Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Investigative Techniques

Study Officials

• Melanie M Taylor, MD

  World Health Organization

  PRINCIPAL INVESTIGATOR

• Nathalie JN Broutet, MD

  World Health Organization

  STUDY DIRECTOR

• Edna O Kara, MD

  World Health Organization

  STUDY CHAIR

Central Study Contacts

Melanie M Taylor, MD

CONTACT

+41 22 791 2172; mtaylor@who.int

Edna O Kara, MD

CONTACT

+41 22 791 2649; karae@who.int

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Offier

Model Details: This is a Phase 1/2 trial to evaluate the efficacy and safety of cefixime for use in treating women with acute syphilis. 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.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.

Study Record Dates

• First Submitted: November 20, 2018
• First Posted: November 23, 2018
• Study Start: November 22, 2019
• Primary Completion: March 30, 2021
• Study Completion: September 30, 2021
• Last Updated: February 5, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Beginning 9 months and ending 24 months following article publication,
• 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.

Locations

BR (1)