Clinical trial protocol to evaluate the efficacy of cefixime in the treatment of early syphilis

Abstract Background: Syphilis rates have been increasing both in the US and internationally with incidence higher among men-who-have-sex-with-men and people living with human immunodeficiency virus (HIV) infection. Currently, benzathine penicillin is the recommended treatment for syphilis in all patients. Global shortages and cost increases in benzathine penicillin call for alternative treatment options. This study evaluates the efficacy of oral cefixime for the treatment of early syphilis. Methods: We are conducting a randomized, multisite, open-label, non-comparative clinical trial in Los Angeles and Oakland, California. Eligible participants are ≥18 years old, with primary, secondary or early latent syphilis (Rapid Plasma Reagin [RPR] titer ≥1:8). Patients with HIV infection must have a viral load ≤200 copies/mL and CD4+ T cell count ≥350 cells/μl during the past 6 months. Participants are randomized to receive either 2.4M IU benzathine penicillin G intramuscularly once or cefixime 400mg orally twice a day for 10 days. Participants return at 3, 6, and 12 months post-treatment for follow-up RPR serological testing. The primary outcome is the proportion of participants who achieve ≥4-fold RPR titer decrease at 3- or 6-months post-treatment.Discussion: Clinical trials evaluating the efficacy of alternative antibiotics to penicillin are urgently needed. Trial Registration: Clinicaltrials.gov, NCT03660488. Registered September 4, 2018, https://clinicaltrials.gov/ct2/show/NCT03660488

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Clinical Trial Protocol to Evaluate the Efficacy of Cefixime in the Treatment of Early Syphilis

10.21203/rs.3.rs-25412/v1 ◽

2020 ◽

Author(s):

Shivani N. Mehta ◽

Chrysovalantis Stafylis ◽

David M. Tellalian ◽

Pamela L. Burian ◽

Cliff M. Okada ◽

...

Keyword(s):

Clinical Trial ◽

Los Angeles ◽

Hiv Infection ◽

Treatment Options ◽

Post Treatment ◽

Penicillin G ◽

Benzathine Penicillin ◽

Open Label ◽

Early Syphilis ◽

Recommended Treatment

Abstract Background: Syphilis rates have been increasing both in the US and internationally with incidence higher among men-who-have-sex-with-men and people living with human immunodeficiency virus (HIV) infection. Currently, benzathine penicillin is the recommended treatment for syphilis in all patients. Global shortages and cost increases in benzathine penicillin call for alternative treatment options. This study evaluates the efficacy of oral cefixime for the treatment of early syphilis. Methods: We are conducting a randomized, multisite, open-label, non-comparative clinical trial in Los Angeles and Oakland, California. Eligible participants are ≥18 years old, with primary, secondary or early latent syphilis (Rapid Plasma Reagin [RPR] titer ≥1:8). Patients with HIV infection must have a viral load ≤200 copies/mL and CD4+ T cell count ≥350 cells/μl during the past 6 months. Participants are randomized to receive either 2.4M IU benzathine penicillin G intramuscularly once or cefixime 400mg orally twice a day for 10 days. Participants return at 3, 6, and 12 months post-treatment for follow-up RPR serological testing. The primary outcome is the proportion of participants who achieve ≥4-fold RPR titer decrease at 3- or 6-months post-treatment.Discussion: Clinical trials evaluating the efficacy of alternative antibiotics to penicillin are urgently needed. Trial Registration: Clinicaltrials.gov, NCT03660488. Registered September 4, 2018, https://clinicaltrials.gov/ct2/show/NCT03660488

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Comparison of serological responses to single-dose azithromycin (2 g) versus benzathine penicillin G in the treatment of early syphilis in HIV-infected patients in an area of low prevalence of macrolide-resistantTreponema palliduminfection

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkv379 ◽

2015 ◽

Vol 71 (3) ◽

pp. 775-782 ◽

Cited By ~ 6

Author(s):

Chia-Jui Yang ◽

Hung-Jen Tang ◽

Sui-Yuan Chang ◽

Szu-Min Hsieh ◽

Kuan-Yeh Lee ◽

...

Keyword(s):

Single Dose ◽

Penicillin G ◽

Benzathine Penicillin ◽

Early Syphilis ◽

Benzathine Penicillin G ◽

Low Prevalence

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Early syphilis: serological treatment response to doxycycline/tetracycline versus benzathine penicillin

The Journal of Infection in Developing Countries ◽

10.3855/jidc.3013 ◽

2014 ◽

Vol 8 (02) ◽

pp. 228-232 ◽

Cited By ~ 7

Author(s):

Jun Li ◽

He-Yi Zheng

Keyword(s):

Success Rate ◽

Serological Test ◽

Treatment Success ◽

Treatment Success Rate ◽

Response To Treatment ◽

Penicillin G ◽

Serological Response ◽

Benzathine Penicillin ◽

College Hospital ◽

Early Syphilis

Introduction: Benzathine penicillin G is the treatment of choice for syphilis, but doxycycline and tetracycline are effective second-line treatments. The objective of this study was to assess the serological response to treatment for early syphilis with benzathine penicillin compared with doxycycline or tetracycline. Methodology: We examined rapid plasma regain (RPR) serological test results of all first-time early syphilis patients in Peking Union Medical College Hospital between 2000 and 2011, comparing treatment with two doses of penicillin to 14-day course of oral doxycycline (100 mg twice daily) or oral tetracycline (500 mg 4 times a day). Results: Of the 641 early syphilis cases with available treatment outcome data, 606 (94.5%) received penicillin and 35 (5.5%) received doxycycline/tetracycline. More than half (52.1%) had secondary syphilis, 13.4% had primary syphilis, and 34.5% had early latent syphilis. A statistically similar serological treatment success rate (p = 0.157) was observed in penicillin-treated patients 91.4% (554/606), when compared with patients treated with doxycycline/tetracycline 82.9% (29/35). Conclusion: Doxycycline/tetracycline had a similar serological treatment success rate when compared to penicillin in the treatment of early syphilis.

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How much penicillin is needed to treat early syphilis in people living with HIV?

Clinical Research in Practice The Journal of Team Hippocrates ◽

10.22237/crp/1625098020 ◽

2021 ◽

Vol 7 (2) ◽

Author(s):

Lily V. Bonadonna

Keyword(s):

Clinical Trial ◽

Single Dose ◽

Randomized Clinical Trial ◽

Barriers To Care ◽

Clinical Decision ◽

People Living With Hiv ◽

Benzathine Penicillin ◽

Clin Infect ◽

Early Syphilis ◽

Living With Hiv

A clinical decision report using: Andrade R, Rodriguez-Barradas MC, Yasukawa K, Villarreal E, Ross M, Serpa JA. Single Dose Versus 3 Doses of Intramuscular Benzathine Penicillin for Early Syphilis in HIV: A Randomized Clinical Trial. Clin Infect Dis. 2017;64(6):759-764. https://doi.org/10.1093/cid/ciw862 to inform treatment of syphilis for a person living with HIV with multiple socioeconomic barriers to care.

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An open-label phase 1 clinical trial of the anti-α4β7 monoclonal antibody vedolizumab in HIV-infected individuals

Science Translational Medicine ◽

10.1126/scitranslmed.aax3447 ◽

2019 ◽

Vol 11 (509) ◽

pp. eaax3447 ◽

Cited By ~ 19

Author(s):

Michael C. Sneller ◽

Katherine E. Clarridge ◽

Catherine Seamon ◽

Victoria Shi ◽

Marek D. Zorawski ◽

...

Keyword(s):

Clinical Trial ◽

Monoclonal Antibody ◽

Hiv Infection ◽

Phase 1 ◽

Single Subject ◽

Lymphoid Tissues ◽

Plasma Viremia ◽

Open Label ◽

Phase 1 Clinical Trial ◽

Open Label Phase

Despite the substantial clinical benefits of antiretroviral therapy (ART), complete eradication of HIV has not been possible. The gastrointestinal tract and associated lymphoid tissues may play an important role in the pathogenesis of HIV infection. The integrin α4β7 facilitates homing of T lymphocytes to the gut by binding to the mucosal addressin cell adhesion molecule-1 (MAdCAM-1) expressed on venules in gut-associated lymphoid tissue. CD4+ T cells with increased expression of α4β7 are susceptible to HIV infection and may be key players in subsequent virus dissemination. Data from nonhuman primate models infected with simian immunodeficiency virus (SIV) have suggested that blockade of the α4β7/MAdCAM-1 interaction may be effective at preventing SIV infection and may have beneficial effects in animals with established viral infection. To explore whether these findings could be reproduced in HIV-infected individuals after interruption of ART, we conducted an open-label phase 1 clinical trial of vedolizumab, a monoclonal antibody against α4β7 integrin. Vedolizumab infusions in 20 HIV-infected individuals were well tolerated with no serious adverse events related to the study drug. After interruption of ART, the median time to meeting protocol criteria to restart therapy was 13 weeks. The median duration of plasma viremia of <400 copies/ml was 5.4 weeks. Only a single subject in the trial experienced prolonged suppression of plasma viremia after interruption of ART. These results suggest that blockade of α4β7 may not be an effective strategy for inducing virological remission in HIV-infected individuals after ART interruption.

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Jarisch-Herxheimer reaction among HIV-positive patients with early syphilis: azithromycin versus benzathine penicillin G therapy

Journal of the International AIDS Society ◽

10.7448/ias.17.1.18993 ◽

2014 ◽

Vol 17 (1) ◽

pp. 18993 ◽

Cited By ~ 9

Author(s):

Mao-Song Tsai ◽

Chia-Jui Yang ◽

Nan-Yao Lee ◽

Szu-Min Hsieh ◽

Yu-Hui Lin ◽

...

Keyword(s):

Penicillin G ◽

Hiv Positive ◽

Benzathine Penicillin ◽

Early Syphilis ◽

Benzathine Penicillin G

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A phase Ib multicenter study of trifluridine/tipiracil (FTD/TPI) in combination with irinotecan (IRI) in patients with advanced recurrent or unresectable gastric and gastroesophageal adenocarcinoma (aGEC) after at least one line of treatment with a fluoropyrimidine and platinum containing regimen.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.tps251 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. TPS251-TPS251

Author(s):

Farshid Dayyani ◽

Kit Tam ◽

Edward Kim ◽

Parvin Keshtmand ◽

Samuel Ejadi ◽

...

Keyword(s):

Peripheral Neuropathy ◽

Treatment Options ◽

Objective Response ◽

Progression Free Survival ◽

Primary Objective ◽

Open Label ◽

Recommended Treatment ◽

Advanced Colon Cancer ◽

Heavily Pretreated ◽

Gastroesophageal Adenocarcinoma

TPS251 Background: In 2L+ aGEC, taxanes +/- ramucirumab or IRI are recommended treatment options. IRI has been tested in multiple single arm and randomized trials in second line (2L)+ aGEC, with reported objective response rates (ORR) in the 15-29% range and median progression-free survival (PFS) of <3 months (mo). Outcomes for aGEC remain poor with a median overall survival (OS) of 9.6 mo and PFS at 6 mo (PFS6) of only 36%. The TAGS trial in third line (3L)+ aGEC showed a significant improvement in OS from 3.6 mo to 5.7 mo with FTD/TPI over placebo. A 2L treatment with taxanes after 1L platinum containing regimens is currently associated with worsening peripheral neuropathy, which often leads to dose reductions, treatment delays, and a reduced quality of life for patients. The feasibility of FTD/TPI combined with IRI (+/- bevacizumab) in a modified 14-day schedule has been published for advanced colon cancer (PMID: 31924737) with no new safety signals while also encouraging activity in a cohort of heavily pretreated patients. Methods: Hypothesis:The combination of FTD/TPI with IRI in 2L+ aGEC is feasible, clinically active, and provides a treatment option which is not associated with development of peripheral neuropathy. Trial Design: 2-center, prospective, open label, non-randomized phase 1b trial. Eligibility: Diagnosis of aGEC, 1+ line of treatment including a fluoropyrimidine/platinum, ECOG 0-2, adequate organ function. Treatment:FTD/TPI 25mg/m2 on days 1-5 and IRI 180mg/m2 on day 1 every 14 days. G-CSF in allowed as needed. Primary objective: Feasibility of the regimen and estimate of efficacy. Primary endpoint: PFS6. Secondary objectives: OS, ORR, adverse events. Total number of pts to be enrolled N=20. Current enrollment (September 2020) N=14. Clinical trial information: NCT04074343.

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UK National Audit of Early Syphilis Management. Clinics audit: screening for and management of early syphilis

International Journal of STD & AIDS ◽

10.1258/095646206776790204 ◽

2006 ◽

Vol 17 (5) ◽

pp. 344-348 ◽

Cited By ~ 1

Author(s):

Hugo McClean ◽

David Daniels ◽

Chris Carne ◽

Paul Bunting ◽

Rob Miller ◽

...

Keyword(s):

Contact Tracing ◽

Penicillin G ◽

Benzathine Penicillin ◽

National Audit ◽

National Guidelines ◽

Procaine Penicillin ◽

Early Syphilis ◽

Benzathine Penicillin G ◽

Management Policies ◽

Dark Ground

Data were provided by 131 clinics, and 56% of cases were managed in clinics in the London regions in 2003. Three clinics (2%) do not routinely screen new patients for syphilis, and 28 clinics (21%) do not routinely screen 'rebook' patients who have had a new partner. More than 80% of clinics routinely conduct cardiovascular and neurological examinations, although chest radiography is only performed by 50% of clinics and lumbar puncture by 13%. Only 19 (14%) clinics indicated not routinely using the recommended procaine penicillin G (PPG) regimen or one- or two-dose benzathine penicillin G (BPG) regimens for early syphilis, with 57% providing two doses of BPG 2.4 g, 40% providing PPG 750 mg for 10 days, and 15% providing one dose of BPG 2.4 g. Only seven clinics (5%) indicated that they provided treatment for early syphilis with PPG that is inferior to that recommended in the national guidelines. Only 18 clinics specified using the recommended dose and duration (or in excess of this) of PPG for neurosyphilis for cases with HIV infection. Provision for management of severe penicillin reaction is good, although few patients are desensitized. All clinics report that contact tracing for early syphilis is provided, and is mainly the responsibility of health advisers. Compared with auditing outcomes, audit of management policies overestimated performance in contact tracing and provision of dark ground microscopy.

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