Pilot study of linezolid for early syphilis treatment

利奈唑胺治疗早期梅毒的初步研究

• 批准号: 10575509
• 负责人: Jeffrey David Klausner
• 金额: $ 23.72万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-11-22 至 2024-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10575509
• 关键词: Address; Adherence; Adult; Aftercare; Allergic; Animals; Antibiotic Therapy; Antibiotics; Bacteria; Benzathine Penicillin; Case Series; Cefixime; Ceftriaxone; Cephalosporins; Cerebrospinal Fluid; Clinic; Clinical; Clinical Research; Clinical Trials; Collection; Control Groups; Country; Data; Data Analyses; Data Collection; Development; Dose; Doxycycline; Drug Kinetics; Drug resistance in tuberculosis; Early treatment; Enrollment; FDA approved; Funding; Generations; Globus Pallidus; Gram-Positive Bacteria; HIV Infections; Hour; Human; Hypersensitivity; In Vitro; Incidence; Individual; Infectious Skin Diseases; Injectable; Injections; International; Intramuscular; Lesion; Linezolid; Minimum Inhibitory Concentration measurement; Modeling; Monitor; Oral; Oral Administration; Oral cavity; Oryctolagus cuniculus; Outcome; Oxazolidinones; Participant; Patients; Penicillin Allergy; Penicillin G; Penicillins; Persons; Peru; Phase; Pilot Projects; Pneumonia; Predisposition; Pregnancy; Randomized; Randomized, Controlled Trials; Recommendation; Regimen; Research; Safety; Sampling; Scheme; Serology; Serology test; Site; Specimen; Streptococcus; Syphilis; System; Testing; Tetracyclines; Time; Toxic effect; Training; Treponema pallidum; United States National Institutes of Health; Vancomycin resistant enterococcus; Work; alternative treatment; arm; bactericide; clinical efficacy; clinical research site; cost; data dissemination; effective therapy; efficacy evaluation; experience; experimental arm; experimental study; follow-up; healing; instrument; men who have sex with men; methicillin resistant Staphylococcus aureus; microbicide; novel; novel strategies; open label; participant enrollment; pilot trial; recruit; research clinical testing; response; success; treatment duration

PROJECT ABSTRACT The proposed pilot project will evaluate the efficacy of linezolid in the treatment of early syphilis. Syphilis rates are increasing both in the US and internationally. Incidence is higher among men who have sex with men and in individuals with HIV infection. Currently, injectable penicillin is used to treat syphilis; however, injectable penicillin is not available in many countries. Doxycycline, tetracycline, and ceftriaxone are alternative treatments for non- pregnant patients who are allergic to penicillin. Although existing treatment alternatives are based on clinical experience, there are a limited number of small clinical trials and case series. Each non-penicillin treatment poses clinical challenges for administration and compliance. Repurposing already approved and safe antibiotics could bring new, safe, and efficacious antibiotic treatment options into the clinic faster and cut down on development costs. This pilot project focuses on studying the potential efficacy of the FDA-approved antibiotic linezolid. In this proposal, we will test the clinical efficacy and microbicidal activity of linezolid to establish its use as a syphilis treatment. We will build upon our successful syphilis clinical studies to conduct a randomized, open- label, non-comparative pilot study to evaluate the efficacy of two linezolid dosing schemes (600mg, twice a day, for ten days or for five days) in patients. We will enroll 60 participants with early syphilis from two clinical sites in Peru. We will follow the participants to monitor clinical progress and serological response (RPR titer) at 7, 30, 90, 180, 270 and 360 days. Our hypothesis is that linezolid will be efficacious in treating early syphilis demonstrated by four-fold decrease in RPR titer, from enrollment to three or six months after treatment administration, and by microbicidal activity against multiple Treponema pallidum isolates. The two specific aims of our proposal are: AIM 1: To evaluate the efficacy of linezolid for the treatment of early syphilis. AIM 2: Evaluate the susceptibility of Treponema pallidum historical and novel strains to linezolid. The two-year project has four phases. Phase I will last four months and will involve the development of study instruments and staff training on recruitment, enrollment, and data collection. Phase II will last 12 months and will involve recruitment and enrollment of patients and collection of clinical specimens. Phase III will last 24 months, but will proceed simultaneously with Phase II, and include the patient follow-up period. Phase IV will last three months and includes data analysis and dissemination.

项目摘要 拟议的试点项目将评估LineZolid在治疗早期梅毒治疗方面的功效。梅毒率 在美国和国际上都在增加。与男人发生性关系的男人的发病率更高 患有艾滋病毒感染的人。目前，可注射的青霉素用于治疗梅毒；但是，可注射的青霉素 在许多国家 /地区不可用。强力霉素，四环素和头孢曲松是非 - 对青霉素过敏的孕妇。尽管现有的治疗替代方法是基于临床的 经验，有数量有限的小型临床试验和病例系列。每种非苯胺素治疗 对管理和合规提出临床挑战。重新利用已经批准和安全的抗生素 可以将新的，安全和有效的抗生素治疗选择带入诊所，并减少 发展成本。该试点项目的重点是研究FDA批准的抗生素的潜在功效 lineZolid。 在此提案中，我们将测试LineZolid的临床疗效和杀生活性，以确定其用作 梅毒治疗。我们将基于成功的梅毒临床研究，以进行随机，开放的 标签，非舒张试验研究，以评估两种lineZolid剂量方案的功效（每天600mg，两次， 患者十天或五天）。我们将在两个临床部位的早期梅毒中注册60名参与者 秘鲁。我们将跟随参与者在7、30，30，30岁的临床进度和血清学反应（RPR滴度）监测 90、180、270和360天。我们的假设是linezolid将有效治疗早期的梅毒 从入学人数到治疗后三到六个月，通过RPR滴度的降低四倍。 给药，并通过对多种曲霉粒分离株的微生物活性。 我们提案的两个具体目的是：目标1：评估linezolid在早期治疗中的功效 梅毒。 AIM 2：评估Treponema Pallidum历史和新型菌株对LineZolid的敏感性。 这个为期两年的项目有四个阶段。第一阶段将持续四个月，并将涉及研究的发展 关于招聘，入学和数据收集的工具和员工培训。第二阶段将持续12个月， 将涉及患者的招募和招募以及临床标本的收集。第三阶段将持续24 几个月，但将与II期同时进行，并包括患者的随访期。第四阶段会 最近三个月包括数据分析和传播。