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

• 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
• 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

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 本项目拟评价头孢克肟（400 mg，每日2次，共10天）的疗效。 与苄星青霉素G（240万单位，肌内注射）相比， 感染在美国和国际上，合成率一直在上升。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，青霉素用于 治疗感染和未感染艾滋病毒的梅毒患者。强力霉素、四环素和头孢曲松是 对青霉素过敏的非妊娠患者的替代治疗。现有的替代治疗方法 基于临床经验，有限数量的小型临床试验和病例系列，但每种都构成了 临床挑战需要新的、安全有效的抗生素治疗选择。 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（400 mg，每日两次，共10天）与 苄星青霉素G（240万单位，肌肉注射）在有和没有艾滋病毒感染的患者。我们将招收 来自美国和秘鲁9个临床研究中心的400名早期梅毒感染受试者。我们将按照 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 假设头孢克肟在治疗梅毒方面不劣于青霉素， 从入组至治疗后6个月的RPR滴度。这是我们的两个具体目标。 提议目的1：评价头孢克肟治疗早期梅毒的有效性， 苄星青霉素目的2：确定参与者中治疗失败的预测因素。 五年计划分四个阶段。第一阶段将持续9个月，将涉及研究的发展 仪器，人员招募培训，入组和数据收集。第二阶段将持续36个月， 包括患者的招募和登记。第三阶段将持续45个月，但将同时开始 作为II期，并将包括患者随访期。第四阶段将持续6个月，在此期间， 将被分析和传播。