Clinical Trial Comparing the Effectiveness of Cefixime Versus Penicillin G for Treatment of Early Syphilis

比较头孢克肟与青霉素 G 治疗早期梅毒疗效的临床试验

基本信息

批准号：
10392825
负责人：
Jeffrey David Klausner
金额：
$ 66.51万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-13 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10392825
关键词：
Address Adherence Aftercare Allergic Antibiotic Therapy Antibiotics Benzathine Penicillin Biological Availability CD4 Positive T Lymphocytes California Case Series Cefixime Ceftriaxone Cell Count Cephalosporins Characteristics Clinical Clinical Markers Clinical Trials Data Data Collection Development Dose Doxycycline Early treatment Effectiveness Enrollment Generations HIV HIV Infections Human Incidence Individual Infection Injectable Injections International Intramuscular Macrolides Monitor Oral Oral cavity Outcome Participant Patients Penicillin Allergy Penicillin G Penicillins Peru Pharmacology Phase Pilot Projects Pregnancy Randomized Recommendation Recording of previous events Regimen Research Review Literature Serology Serum Symptoms Syphilis Tetracyclines Time Toxic effect Training Treatment Failure United States Food and Drug Administration Viral Load result alternative treatment arm base beta-Lactams clinical research site compare effectiveness cost design effective therapy effectiveness evaluation efficacy evaluation experience experimental arm follow-up instrument men who have sex with men novel novel strategies open label participant enrollment recruit response study population treatment arm treatment duration

项目摘要

PROJECT ABSTRACT The proposed project is designed to evaluate the effectiveness of cefixime (400mg, twice a day, for 10 days) compared to benzathine penicillin G (2.4 million units, intramuscularly) in patients with and without HIV infection. Syphilis rates have been increasing both in the US and internationally. Incidence is higher among men-who-have-sex-with-men and more importantly in individuals with HIV infection. Currently, penicillin is used to treat syphilis in patients with and without HIV infection. Doxycycline, tetracycline and ceftriaxone are alternative treatments for non-pregnant patients who are allergic to penicillin. Existing treatment alternatives are based on clinical experience, a limited number of small clinical trials, and case series, but each poses clinical challenges. New, safe and efficacious antibiotic treatment options are needed. In this proposal, we will build upon our successful pilot study to conduct a randomized, multisite, open-label, non- inferiority clinical trial to evaluate the effectiveness of cefixime (400mg, twice a day, for 10 days) compared to benzathine penicillin G (2.4 million units, intramuscularly) in patients with and without HIV infection. We will enroll 400 participants with early syphilis infection from 9 clinical sites in the U.S. and Peru. We will follow the participants to monitor clinical progress and serological response (RPR titer) every 3 months for 9 months. Our hypothesis is that cefixime will be non-inferior to penicillin in treating syphilis, shown as a 4-fold decrease in RPR titer from enrollment to 6-months after treatment administration. These are the two specific aims of our proposal. AIM 1: Evaluate the effectiveness of cefixime in the treatment of early syphilis when compared to benzathine penicillin G. AIM 2: Determine the predictors of treatment failure among participants. The 5 year project has 4 phases. Phase I will last 9 months and will involve the development of study instruments, staff training on recruitment, enrollment, and data collection. Phase II will last 36 months and will involve recruitment and enrollment of patients. Phase III which will last 45 months, but will start simultaneously as stage II, and will include the patient follow-up period. Phase IV will last 6 months and in that time, the data will be analyzed and disseminated.

项目摘要拟议项目旨在评估头孢克肟（400mg，每天两次，持续10天）的有效性在感染和未感染 HIV 的患者中与苄星青霉素 G（240 万单位，肌肉注射）进行比较感染。在美国和国际上，梅毒发病率一直在上升。其中发病率较高男男性行为者，更重要的是艾滋病毒感染者。目前使用的是青霉素用于治疗感染或未感染艾滋病毒的患者的梅毒。多西环素、四环素和头孢曲松是对青霉素过敏的非怀孕患者的替代治疗。现有的治疗替代方案基于临床经验、有限数量的小型临床试验和病例系列，但每项都提出临床挑战。需要新的、安全且有效的抗生素治疗方案。在本提案中，我们将在成功的试点研究的基础上进行一项随机、多中心、开放标签、非评价头孢克肟（400mg，每天两次，持续 10 天）与苄星青霉素 G（240 万单位，肌肉注射）用于感染或未感染 HIV 的患者。我们将报名来自美国和秘鲁 9 个临床中心的 400 名早期梅毒感染参与者。我们将遵循参与者每 3 个月监测一次临床进展和血清学反应（RPR 滴度），持续 9 个月。我们的假设头孢克肟在治疗梅毒方面不逊于青霉素，表现为 4 倍的减少从入组到治疗后 6 个月的 RPR 滴度。这是我们的两个具体目标提议。目标 1：与其他药物相比，评估头孢克肟治疗早期梅毒的有效性苄星青霉素 G。目标 2：确定参与者治疗失败的预测因素。该项目为期5年，分为4个阶段。第一阶段将持续 9 个月，并将涉及研究的发展工具、招聘、注册和数据收集方面的工作人员培训。第二阶段将持续36个月，涉及患者的招募和登记。第三阶段将持续 45 个月，但将同时开始作为第二阶段，并将包括患者随访期。第四阶段将持续 6 个月，在此期间，数据将被分析和传播。