RIFAPENTINE FOR RELAPSE AMONG HIV SEROPOSITIVE & SELECTED SERONEGATIVE

利福喷丁治疗 HIV 血清阳性者复发

• 批准号: 6415246
• 负责人: CAROL S DUKES-HAMILTON
• 金额: $ 29.31万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-12-01 至 2001-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6415246
• 关键词: HIV infections; antitubercular agents; clinical research; comorbidity; drug screening /evaluation; human subject; human therapy evaluation; pharmacokinetics; relapse /recurrence; rifamycins; tuberculosis

Since 1995, Duke University Medical Center and the Durham VAMC have been participating in a CDC-sponsored, multi-center, Phase 3 efficacy and safety trial of a new rifamycin derivative, rifapentine, for the treatment of pulmonary M. tuberculosis in the continuation phase of therapy (IRB Number 1861-97-12R3). The purpose of this multi-center sub-study of the U.S. CDC Rifapentine Clinical Trial is to evaluate drug pharmacokinetics and risk factors for relapse among four patient groups: 1. HIV-positive patients, 2. those who failed TB treatment or relapsed, 3. HIV-negative controls, matched to each HIV-negative failure or relapse, and 4. all HIV-negative participants on study-phase therapy in the Rifapentine Clinical Trial (referred to as the "prospective group"). Specific objectives are: 1. To study INH and rifamycin pharmacokinetics, 2. To define INH acetylator status, 3. To determine the bioavailability of INH, rifampin, and rifapentine, and 4. To compare the use of urine and blood for pharmacokinetic screening. Methods: At the beginning of the study, only the first two groups from the Rifapentine Clinical Trial were included; a later amendment added the other two groups. Potential candidates have included 3 HIV-positive patients, one failure, one relapse, and those receiving study-phase therapy. The study is being done on the General Clinical Research Center (GCRC), on an outpatient and inpatient basis. After informed consent has been obtained and if pre-study liver function tests are within the enrollment parameters, each patient receives a single dose of INH and either rifampin or rifapentine (whichever they received in the study phase of the Rifapentine Clinical Trial). Patients on protease inhibitors do not receive either rifamycin. For patients currently receiving therapy in the Rifapentine Clinical Trial, blood is drawn just prior to the medication dose. Blood is drawn at 1, 2, 5, and 24 hours post dose. Patients who receive rifapentine also have blood drawn at 48 hours post dose. Blood is also drawn for INH acetylator status, CBC, chemistries, and for those HIV-positive, for CD4 count and HIV viral load. Urine is collected at 5 and 24 hours post dose. The medical record is reviewed and patients interviewed regarding concomitant medications, gastrointestinal symptoms, and meals. Patients are asked to duplicate, as much as possible, the meals and medications they took during study-phase therapy. If they are taking new medications, we will discuss with their physician whether the medications can be temporarily discontinued. Progress Report: Four patients have been enrolled to date. Two were HIV-positive (one on a protease inhibitor) and two were prospective patients. Three patients were African-American males and one was an African-American female. All tolerated the study procedures without adverse events. There may be patients enrolled in the next year, if there are new failures, relapses, or eligible prospective patients. Significance: This study addresses an important public health risk - tuberculosis in HIV infected individuals.

自 1995 年以来，杜克大学医学中心和达勒姆 VAMC 一直参与一项由 CDC 赞助的多中心 3 期疗效和安全性试验，试验的目的是研究新型利福霉素衍生物利福喷汀，用于治疗肺结核分枝杆菌的继续治疗阶段（IRB 编号 1861-97-12R3）。美国疾病预防控制中心利福喷丁临床试验的这项多中心子研究的目的是评估四个患者组的药物药代动力学和复发危险因素：1. HIV 阳性患者，2. 结核病治疗失败或复发的患者，3. HIV 阴性对照，与每个 HIV 阴性失败或复发相匹配，4. 所有在研究阶段治疗的 HIV 阴性参与者 利福喷丁临床试验（简称“前瞻性组”）。具体目标是： 1. 研究 INH 和利福霉素的药代动力学， 2. 确定 INH 乙酰化状态， 3. 确定 INH、利福平和利福喷汀的生物利用度，以及 4. 比较尿液和血液用于药代动力学筛查的情况。方法：在研究开始时，仅纳入利福喷丁临床试验的前两组；后来的修正案增加了其他两组。潜在候选者包括 3 名 HIV 阳性患者、1 名失败患者、1 名复发患者以及接受研究阶段治疗的患者。该研究是在普通临床研究中心（GCRC）的门诊和住院基础上进行的。在获得知情同意后，如果研究前肝功能测试在入组参数范围内，每位患者将接受单剂量的 INH 和利福平或利福喷汀（以利福喷汀临床试验研究阶段接受的为准）。服用蛋白酶抑制剂的患者不接受利福霉素。对于目前正在接受利福喷丁临床试验治疗的患者，将在服药前抽血。给药后1、2、5和24小时抽取血液。接受利福喷汀治疗的患者也在服药后 48 小时抽血。还抽血检查 INH 乙酰化状态、全血细胞计数 (CBC)、化学成分，以及 HIV 阳性者的 CD4 计数和 HIV 病毒载量。在给药后5小时和24小时收集尿液。审查病历并就伴随药物、胃肠道症状和膳食对患者进行访谈。要求患者尽可能重复他们在研究阶段治疗期间服用的膳食和药物。如果他们正在服用新药物，我们将与他们的医生讨论是否可以暂时停药。进展报告：迄今为止已入组四名患者。两名患者是艾滋病毒阳性（一名正在服用蛋白酶抑制剂），两名是潜在患者。三名患者是非裔美国男性，一名是非裔美国女性。所有人都耐受研究程序，没有发生不良事件。如果有新的失败、复发或符合条件的潜在患者，明年可能会有患者入组。意义：这项研究解决了一个重要的公共卫生风险——艾滋病毒感染者的结核病。