TBTC Study 26: Effectiveness and Tolerability of Weekly Rifapentine/Isoniazid for 3 Months Versus Daily Isoniazid for 9 Months for the Treatment of Latent Tuberculosis Infection
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 8,053
- 试验地点
- 26
- 主要终点
- Cumulative Rate of Culture-Confirmed TB Disease in Participants ≥18 Years of Age AND Culture-Confirmed or Probable (Clinical) TB Disease in Participants Less Than [<]18 Years of Age at 33 Months After Enrollment
研究概览
简要总结
Open-label, multi-center, Phase III clinical trial to compare the effectiveness and tolerability of a three-month (12-dose) regimen of weekly rifapentine and isoniazid (3RPT/INH) to the effectiveness of a nine-month (270-dose)regimen of daily isoniazid (9INH) to prevent tuberculosis (TB) among high-risk tuberculin skin-test reactors, including children and HIV-infected persons, who require treatment of latent TB infection (LTBI).
详细描述
The PRIMARY objective of this open-label Phase III clinical trial is to compare the effectiveness of a three-month (12-dose) regimen of weekly rifapentine and isoniazid (3RPT/INH) to the effectiveness of a nine-month (270-dose) regimen of daily isoniazid (9INH) to prevent tuberculosis (TB) among high-risk tuberculin skin-test reactors, including children and HIV-infected persons, who require treatment of latent TB infection (LTBI). The 3RPT/INH regimen will be given under direct observation and the 9INH regimen will be self-administered.
SECONDARY Objectives:
- Compare the rates of drug discontinuation due to adverse drug reactions associated with 3RPT/INH and 9INH.
- Compare the rates of drug discontinuation for any reason associated with 3RPT/INH and 9INH.
- Compare the rates of any grade 3, 4, or 5 drug toxicity associated with 3RPT/INH and 9INH.
- Compare treatment completion rates of 3RPT/INH and 9INH. Compare the efficacy (i.e., among persons who complete study-phase therapy) of 3RPT/INH and 9INH.
- Compare the effectiveness and tolerability of 3RPT/INH and 9INH in HIV-infected persons.
- Compare the effectiveness and tolerability of 3RPT/INH and 9INH in children < 18 years old.
- Compare the rates of methadone withdrawal associated with 3RPT/INH and 9INH among persons concomitantly receiving methadone.
- Describe patterns of antibiotic resistance among M. tuberculosis isolates in patients who develop TB despite treatment of latent infection.
Amendment of the study protocol to allow extension of enrollment to children < 12 years old and HIV-infected persons:
For assessment of the primary outcome, development of TB, a sample size of approximately 4,000 persons per arm will be required. To assess tolerability (one of the secondary outcomes) in sub-groups, children less than 12 years old and HIV-infected persons, a sample size of 644 per strata will be required. A sample size of 8,053 patients for the primary outcome was reached on February 15, 2008 (with expected follow-up completion time in 2010), leaving approximately 454 additional young children and 200 HIV-infected persons to be enrolled to achieve the targets of 644 for each group. The additional data on tolerability in those sub-groups will available for analysis in 2013.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Daily Isoniazid
Isoniazid (INH) daily for 9 months (240 to 270 total doses).
干预措施: Isoniazid (INH) daily for 9 months (Drug)
Weekly Isoniazid / Rifapentine
Isoniazid / Rifapentine (RPT/INH) weekly for 3 months (11 to 12 total doses) given by Directly Observed Therapy (DOT)
干预措施: RPT + INH once weekly for 3 months given by DOT (Drug)
结局指标
主要结局
Cumulative Rate of Culture-Confirmed TB Disease in Participants ≥18 Years of Age AND Culture-Confirmed or Probable (Clinical) TB Disease in Participants Less Than [<]18 Years of Age at 33 Months After Enrollment
时间窗: Baseline up to Month 33
Cumulative TB disease rate defined as number of participants ≥18 years old with culture-confirmed TB disease (defined as positive culture for Mycobacterium tuberculosis \[MTB\]) and those \<18 years old with probable (clinical) TB disease (defined as objective evidence of clinical TB disease \[cough, fever, night sweats, weight loss, or hemoptysis\] based on history or physical exam plus radiograph, computed tomography \[CT\] scan, other diagnostic tests PLUS response to antituberculosis therapy AND objective improvement of radiograph or other diagnostic tests; OR evidence of granuloma with organism positive for acid-fast bacilli \[AFB\], or caseating granulomata at autopsy or biopsy) between enrollment and the 990th Day of the Trial (33 months after enrollment, or end of the trial) per 100 participants with (w/)33 months of follow-up calculated using survival analysis methods (Kaplan-Meier approach).
次要结局
- Cumulative Rate of Culture-Confirmed or Probable (Clinical) TB Disease (Regardless of Age) At 33 Months After Enrollment(Baseline up to 33 Months)
- Cumulative Rate of Culture-Confirmed TB Disease in Participants ≥18 Years of Age AND Culture-Confirmed or Probable (Clinical) TB Disease in Participants <18 Years of Age at 24 Months Following Completion of Study Therapy(Baseline up to Month 27 (3RPT/INH) or Month 33 (9INH))
- Cumulative Rate of Culture-Confirmed or Probable TB Disease in HIV-Infected Participants Within 33 Months After Enrollment(Baseline to Month 33)
- Percentage of Participants With Drug Discontinuation Due to Adverse Drug Reactions Associated With 3RPT/INH or 9INH(Baseline up to 60 days after the last dose of study drug (Month 5 [3RPT/INH] or Month 11 [9INH]))
- Percentage of Patients With Grade 3 or 4 Drug Toxicities Associated With 3RPT/INH or 9INH(Baseline up to 60 days after the last dose of study drug (Month 5 [3RPT/INH] or Month 11 [9INH]))
- Percentage of Participants With Death Due to Any Cause(Baseline up to Month 35)
- Percentage of Participants With Drug Discontinuation for Any Reason Associated With 3RPT/INH or 9INH(Baseline up to Month 3 (3RPT/INH) or Month 9 (9INH))
- Percentage of Participants With Methadone Withdrawal Associated With 3RPT/INH and 9INH Among Participants Receiving Concomitant Methadone(Baseline to Month 33)
- Percentage of Participants Who Completed the Treatment Regimen(Baseline up to Month 3 (3RPT/INH) or Month 9 (9INH))
- Cumulative Rate of Culture-Confirmed TB Disease in Participants ≥18 Years of Age AND Culture Confirmed or Probable (Clinical) TB Disease Among Participants <18 Years of Age Who Completed Study Phase Therapy Within 33 Months of Enrollment(Baseline up to Month 33)
- Percentage of Participants With Resistance to Study Medications in Isolates of MTB From Participants Who Developed Active TB Disease Within 33 Months of Enrollment(Baseline up to Month 33)
- Cumulative Rate of HIV-Infected Participants With Culture-Confirmed or Probable TB Disease at 24 Months After Completion of Study Therapy(Baseline up to Month 27 (3RPT/INH) or Month 33 (9INH))
- Cumulative Rate of Participants <18 Years Old With Culture-Confirmed or Probable (Clinical) TB Disease Within 33 Months of Enrollment(Baseline up to Month 33)
- Cumulative Rate of Participants <12 Years Old With Culture-Confirmed or Probable (Clinical) TB Disease Within 33 Months of Enrollment(Baseline up to Month 33)