A Phase II Randomized, Open-label Trial of a Rifapentine Plus Moxifloxacin-Based Regimen for Intensive Phase Treatment of Smear-Positive Pulmonary Tuberculosis
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 121
- 试验地点
- 3
- 主要终点
- To Compare, by Treatment Group, the Percentage of Patients With a Negative Sputum Culture at the End of Intensive Phase Therapy.
研究概览
简要总结
Although effective therapy for tuberculosis is available, TB continues to cause significant problems worldwide, and rates of multi-drug resistant (MDR) TB cases are on the rise. A major obstacle to the control of TB is poor adherence with lengthy (usually 6 months) and complicated treatment regimens. Incomplete TB treatment can lead to serious consequences such as increased severity of illness and death, prolonged infectiousness and transmission in the community, and the development of drug resistance. The development of new treatment strategies with more stronger drugs could lead to shorter and simpler regimens. A TB treatment regimen that allowed treatment duration to be meaningfully decreased would have important public health implications.
This trial will compare the effect and safety of a new oral regimen to that of the standard regimen for the first phase of treatment for pulmonary tuberculosis.
The experimental regimen will consist of the following:
- Two months of isoniazid, rifapentine, pyrazinamide and moxifloxacin (HPZM) administered once daily. Pyridoxine (vitamin B6) will be given with each dose of isoniazid.
The standard control intensive phase regimen will consist of the following:
- Two months of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) administered once daily. Pyridoxine (vitamin B6) will be given with each dose of isoniazid.
Following intensive phase therapy (the study phase), all patients will be treated with a non-experimental continuation phase regimen.
In mice, the combination of Moxifloxacin and Rifapentine have cured the animals significantly faster than the standard regimen and this study will be the first step to see if the potential is also there in humans.
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
- None
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Presumptive diagnosis of sputum smear-positive pulmonary TB.
- •Age: ≥18 years
- •Seven (7) or fewer days of multidrug therapy for TB disease in the preceding 6 months.
- •Seven (7) or fewer days of fluoroquinolone therapy in the preceding 3 months.
- •Documentation of HIV infection status.
- •For HIV seropositive individuals, a CD4 T lymphocyte count of greater than or equal to 200 cells/mm
- •Documentation of study baseline laboratory parameters done at, or ≤ 14 days prior to screening:
- •AST less than or equal to 2.5 times upper limit of normal.
- •Total bilirubin level less than 2.5 times upper limit of normal.
- •Creatinine level less than 2 times upper limit of normal.
- •Hemoglobin level of at least 8.0 g/dl.
- •Platelet count of at least 75,000 mm
- •Potassium level of at least 3.
- •Negative pregnancy test (women of childbearing potential).
- •Karnofsky score of at least 60 (requires occasional assistance but is able to care for most of his/her needs).
- •Male or nonpregnant, nonnursing female.
- •Provision of informed consent.
排除标准
- •CD4 count < 200 cells/cu mm.
- •Presence of active AIDS-related opportunistic infection (other than TB) or active AIDS-related malignancy.
- •Known intolerance to any of the study drugs.
- •Concomitant disorders or conditions for which any of the study drugs is contraindicated. These include severe hepatic damage, acute liver disease of any cause, and acute uncontrolled gouty arthritis.
- •Inability to take oral medication.
- •Central nervous system TB.
- •Pulmonary silicosis.
- •Current or planned therapy, during study phase (intensive phase of TB treatment), with any one or more of the following drugs: quinidine, procainamide, amiodarone, sotalol, disopyramide, terfenadine, cisapride, erythromycin, clarithromycin, phenothiazines, haloperidol, olanzapine, ziprasidone, tricyclic antidepressants, chronic corticosteroids administered either orally or intravenously, chronic fluconazole,chronic itraconazole, chronic ketoconazole, oral or intravenous tacrolimus, oral or intravenous cyclosporine, HIV protease inhibitor, HIV non-nucleoside reverse transcriptase inhibitor.
- •Concurrent severe and/or uncontrolled medical or psychiatric condition that, in the opinion of the investigator, could cause unacceptable safety risks or compromise compliance with the protocol.
- •Unable or unwilling to receive directly observed therapy and/or adhere with follow-up (e.g. due to residence remote from the study site).
- •Refusal of consent.
研究组 & 干预措施
1
Two months of isoniazid, rifapentine, pyrazinamide and moxifloxacin (HPZM) administered once daily. Pyridoxine (vitamin B6) will be given with each dose of isoniazid.
干预措施: Rifapentine, Moxifloxacin, Pyrazinamide, Isoniazid (Drug)
2
Two months of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) administered once daily. Pyridoxine (vitamin B6) will be given with each dose of isoniazid.
干预措施: Isoniazid, Rifampin, Pyrazinamide, Ethambutol (Drug)
结局指标
主要结局
To Compare, by Treatment Group, the Percentage of Patients With a Negative Sputum Culture at the End of Intensive Phase Therapy.
时间窗: Week 8
LJ culture conversion
To Compare the Safety and Tolerability of the 2 Intensive Phase Regimens.
时间窗: Weekly or more frequent
Study was prematurely terminated and data was not collected for this outcome measure.
次要结局
未报告次要终点