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

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.

Timeline

Start

2019-11-22

Primary completion

2021-03-30

Completion

2021-09-30

Publications

• Background 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.
• Background WHO. WHO guidelines for the treatment of Treponema pallidum (syphilis). http://wwwwhoint/reproductivehealth/publications/rtis/syphilis-treatment-guidelines/en/. 2016.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Drugs

Indications