TBTC Study 29: Evaluation of a Rifapentine-containing Regimen for Intensive Phase Treatment of Pulmonary Tuberculosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 334
- 试验地点
- 29
- 主要终点
- Participants With Negative Sputum Culture at 8 Weeks
研究概览
简要总结
This Phase 2, multicenter, open-label clinical trial evaluated the antimicrobial activity and safety of rifapentine-containing regimens during the intensive phase of pulmonary tuberculosis treatment.
Participants were randomized to receive either a standard rifampin-based regimen (RHZE) or a rifapentine-substituted regimen (PHZE). An extension study evaluated higher daily doses of rifapentine (10, 15, and 20 mg/kg).
The primary endpoint was sputum culture conversion at 8 weeks. Secondary outcomes included time to culture conversion, safety, and treatment discontinuation.
详细描述
This Phase 2, prospective, multicenter, open-label clinical trial evaluated the antimicrobial activity and safety of rifapentine-containing regimens during the intensive phase of pulmonary tuberculosis treatment.
In the main study, adult participants with suspected pulmonary tuberculosis were randomized to receive either a standard intensive-phase regimen consisting of rifampin, isoniazid, pyrazinamide, and ethambutol (RHZE), or an experimental regimen in which rifapentine (10 mg/kg) was substituted for rifampin (PHZE). Treatment was administered five days per week under direct observation for 8 weeks.
The study extension evaluated higher daily doses of rifapentine (10 mg/kg, 15 mg/kg, and 20 mg/kg) in combination with isoniazid, pyrazinamide, and ethambutol, compared to the standard rifampin-based regimen. In the extension, treatment was administered seven days per week.
The primary efficacy endpoint was the proportion of participants with negative sputum cultures at completion of the intensive phase. Secondary endpoints included time to culture conversion, safety and tolerability, and rates of treatment discontinuation.
Following completion of the intensive phase, participants received standard continuation-phase tuberculosis treatment per guidelines.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Suspected pulmonary tuberculosis with acid-fast bacilli in a stained smear of expectorated or induced sputum.
- •Willingness to have HIV testing performed, if HIV serostatus is not known or if the last documented negative HIV test was more than 3 months prior to enrollment.
- •5 (five) or fewer days of multidrug therapy for tuberculosis disease in the 6 months preceding initiation of study drugs.
- •7 (seven) or fewer days of fluoroquinolone therapy in the 30 days preceding initiation of study drugs.
- •Age >= 18 years
- •Karnofsky score of at least 60 (requires occasional assistance but is able to care for most of his/her needs; see Appendix B)
- •Signed informed consent
- •Women of child-bearing potential must agree to practice an adequate (barrier) method of birth control or to abstain from heterosexual intercourse during study therapy.
- •Laboratory parameters done within 14 days prior to, enrollment:
- •Serum or plasma alanine aminotransferase (ALT) activity ≤ 3 times the upper limit of normal
- •Serum or plasma total bilirubin level ≤ 2.5 times the upper limit of normal
- •Serum or plasma creatinine level ≤ 2 times the upper limit of normal
- •Complete blood count with hemoglobin level of at least 7.0 g/dL
- •Complete blood count with platelet count of at least 100,000/mm3
- •Negative pregnancy test (women of childbearing potential)
排除标准
- •Pregnant or breast-feeding
- •Known intolerance or allergy to any of the study drugs
- •Concomitant disorders or conditions for which isoniazid (INH), rifamycins, pyrazinamide (PZA), or ethambutol (EMB) are contraindicated. These include severe hepatic damage, acute liver disease of any cause, and acute uncontrolled gouty arthritis.
- •Current or planned therapy, during the intensive phase of TB therapy, with combination antiretroviral therapy for HIV, or with cyclosporine or tacrolimus. Cyclosporine and tacrolimus have unacceptable interactions with rifamycins.
- •Pulmonary silicosis
- •Central nervous system TB
- •Weight < 40 kg or > 85 kg
研究组 & 干预措施
Standard TB Treatment (RHZE): Rifampin 10 mg/kg Daily for 8 Weeks
rifampin, isoniazid, pyrazinamide, ethambutol
干预措施: rifapentine (Drug)
Rifapentine 10 mg/kg Daily TB Treatment (PHZE) for 8 Weeks
rifapentine 10 mg/kg, isoniazid, pyrazinamide, ethambutol
干预措施: rifapentine 10 mg/kg (Drug)
Rifapentine 15 mg/kg Daily TB Treatment (PHZE) for 8 Weeks
rifapentine 15 mg/kg, isoniazid, pyrazinamide, ethambutol
干预措施: rifapentine 15 mg/kg (Drug)
Rifapentine 20 mg/kg Daily TB Treatment (PHZE) for 8 Weeks
rifapentine 20 mg/kg, isoniazid, pyrazinamide, ethambutol
干预措施: rifapentine 20 mg/kg (Drug)
结局指标
主要结局
Participants With Negative Sputum Culture at 8 Weeks
时间窗: 8 weeks.
Proportion of participants with negative Mycobacterium tuberculosis sputum cultures at completion of the 8-week intensive phase of treatment.
Participants Who Discontinued Treatment During Intensive Phase
时间窗: 8 weeks
Number of participants who permanently discontinued assigned study treatment for any reason during the first 8 weeks.
次要结局
未报告次要终点