Rifapentine- And Moxifloxacin-Containing Short-Course Regimens for Mild Spinal Tuberculosis: A Multicenter, Randomized, Non-inferiority Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- TB-recurrence rate of spinal tuberculosis at 24 months after completion of treatment.
研究概览
简要总结
To evaluate the non-inferiority in efficacy between the rifapentine- and moxifloxacin-containing short-course regimens (with rifampicin replaced by rifapentine and ethambutol replaced by moxifloxacin, while isoniazid and pyrazinamide remaining the same as the empirical regimen) and the empirical long-course regimen, so as to determine whether it is possible to shorten the treatment duration to 26 weeks for patients with mild spinal tuberculosis.
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 12 years.
- •Based on the medical history, clinical manifestations, radiological, laboratory tests and possible histological samples, the diagnostic criteria are met and judged to be mild spinal tuberculosis.
- •Laboratory test values are completed within 14 days prior to screening.
- •Women of child-bearing potential who are not surgically sterilized must agree to practice a barrier method of contraception or abstain from heterosexual intercourse during study drug treatment.
- •For women of childbearing potential, a negative pregnancy test at or within seven (7) days prior to screening.
- •Karnofsky score greater than or equal to
- •A verifiable address or residence location that is readily accessible for visiting, and willingness to inform the study team of any change of address during the treatment and follow-up period.
- •Written informed consent.
排除标准
- •Exclusions Before Randomization:
- •Pregnant or breast-feeding.
- •Unable to take oral medications.
- •Previously enrolled in similar studies.
- •With spinal tumors or metastatic tumors.
- •Patients with mental disorders and cognitive dysfunction.
- •Received any investigational drug in the past 3 months.
- •More than five (5) days of treatment directed against active tuberculosis within 6 months preceding initiation of study drugs.
- •More than five (5) days of systemic treatment with any one or more of the following drugs within 30 days preceding initiation of study drugs: Isoniazid, rifampin, rifambutin, rifabentine, ethambutol, pyrazinamide, kanamycin, amikacin, streptomycin, capreomycin, moxifloxacin, levofloxacin, gatifloxacin, ofloxacin, ciprofloxacin, other fluoroquinolones, ethionamide, prothionamide, cycloserine, terizidone, para-aminosalicylic acid, linezolid, clofazimine, delamanid or bedaquiline.
- •Known history of prolonged QT syndrome.
- •Weight less than 40.0 kg.
- •Known allergy or intolerance to any of the study medications.
- •Individuals will be excluded from enrollment if, at the time of enrollment, their M. tuberculosis isolate is already known to be resistant to any one or more of the following: rifampin, isoniazid, pyrazinamide, ethambutol, or fluoroquinolones.
- •Other medical conditions, that, in the investigator's judgment, make study participation not in the individual's best interest.
- •Exclusions After Randomization:
- •No M. tuberculosis is identified in the screening, baseline, and week 2 samples.
- •Mycobacterium tuberculosis grown from or tested by molecular assays (Xpert MTB / RIF) in samples obtained before or after the study are determined to be resistant to isoniazid, rifampicin, or fluoroquinolones.
研究组 & 干预措施
Empirical long course regimen
Drug: Rifampicin, once daily, 600 mg, administered for 52 weeks. Drug: Isoniazid, once daily, 300 mg, administered for 52 weeks. Drug: Pyrazinamide, once daily, dosage adjusted based on body weight: 1000 mg for < 55 kg, 1500 mg for ≥ 55-75 kg, and 2000 mg for > 75 kg, administered for the first 8 weeks.
Drug: Ethambutol, once daily, dosage adjusted based on body weight: 800 mg for < 55 kg, 1200 mg for ≥ 55-75 kg, and 1600 mg for > 75 kg, administered for the first 8 weeks.
干预措施: Rifampin (Drug)
Empirical long course regimen
Drug: Rifampicin, once daily, 600 mg, administered for 52 weeks. Drug: Isoniazid, once daily, 300 mg, administered for 52 weeks. Drug: Pyrazinamide, once daily, dosage adjusted based on body weight: 1000 mg for < 55 kg, 1500 mg for ≥ 55-75 kg, and 2000 mg for > 75 kg, administered for the first 8 weeks.
Drug: Ethambutol, once daily, dosage adjusted based on body weight: 800 mg for < 55 kg, 1200 mg for ≥ 55-75 kg, and 1600 mg for > 75 kg, administered for the first 8 weeks.
干预措施: Isoniazid (Drug)
Empirical long course regimen
Drug: Rifampicin, once daily, 600 mg, administered for 52 weeks. Drug: Isoniazid, once daily, 300 mg, administered for 52 weeks. Drug: Pyrazinamide, once daily, dosage adjusted based on body weight: 1000 mg for < 55 kg, 1500 mg for ≥ 55-75 kg, and 2000 mg for > 75 kg, administered for the first 8 weeks.
Drug: Ethambutol, once daily, dosage adjusted based on body weight: 800 mg for < 55 kg, 1200 mg for ≥ 55-75 kg, and 1600 mg for > 75 kg, administered for the first 8 weeks.
干预措施: Pyrazinamide (Drug)
Empirical long course regimen
Drug: Rifampicin, once daily, 600 mg, administered for 52 weeks. Drug: Isoniazid, once daily, 300 mg, administered for 52 weeks. Drug: Pyrazinamide, once daily, dosage adjusted based on body weight: 1000 mg for < 55 kg, 1500 mg for ≥ 55-75 kg, and 2000 mg for > 75 kg, administered for the first 8 weeks.
Drug: Ethambutol, once daily, dosage adjusted based on body weight: 800 mg for < 55 kg, 1200 mg for ≥ 55-75 kg, and 1600 mg for > 75 kg, administered for the first 8 weeks.
干预措施: Ethambutol (Drug)
Short-course regimen
Drug: Rifapentine, once daily, dosage adjusted based on body weight: 750 mg for ≤41.2 kg, 900 mg for >41.3-48.7 kg, 1050 mg for > 48.8-56.2 kg, 1200 mg for ≥ 56.3 kg, administered for 26 weeks.
Drug: Moxifloxacin, once daily, 400 mg, administered for 26 weeks. Drug: Isoniazid, once daily, 300 mg, administered for 26 weeks. Drug: Pyrazinamide, once daily, dosage adjusted based on body weight: 1000 mg for < 55 kg, 1500 mg for ≥ 55-75 kg, and 2000 mg for >75 kg, administered for the first 8 weeks.
干预措施: Isoniazid (Drug)
Short-course regimen
Drug: Rifapentine, once daily, dosage adjusted based on body weight: 750 mg for ≤41.2 kg, 900 mg for >41.3-48.7 kg, 1050 mg for > 48.8-56.2 kg, 1200 mg for ≥ 56.3 kg, administered for 26 weeks.
Drug: Moxifloxacin, once daily, 400 mg, administered for 26 weeks. Drug: Isoniazid, once daily, 300 mg, administered for 26 weeks. Drug: Pyrazinamide, once daily, dosage adjusted based on body weight: 1000 mg for < 55 kg, 1500 mg for ≥ 55-75 kg, and 2000 mg for >75 kg, administered for the first 8 weeks.
干预措施: Rifapentine (RPT) (Drug)
Short-course regimen
Drug: Rifapentine, once daily, dosage adjusted based on body weight: 750 mg for ≤41.2 kg, 900 mg for >41.3-48.7 kg, 1050 mg for > 48.8-56.2 kg, 1200 mg for ≥ 56.3 kg, administered for 26 weeks.
Drug: Moxifloxacin, once daily, 400 mg, administered for 26 weeks. Drug: Isoniazid, once daily, 300 mg, administered for 26 weeks. Drug: Pyrazinamide, once daily, dosage adjusted based on body weight: 1000 mg for < 55 kg, 1500 mg for ≥ 55-75 kg, and 2000 mg for >75 kg, administered for the first 8 weeks.
干预措施: Moxifloxacin (Drug)
Short-course regimen
Drug: Rifapentine, once daily, dosage adjusted based on body weight: 750 mg for ≤41.2 kg, 900 mg for >41.3-48.7 kg, 1050 mg for > 48.8-56.2 kg, 1200 mg for ≥ 56.3 kg, administered for 26 weeks.
Drug: Moxifloxacin, once daily, 400 mg, administered for 26 weeks. Drug: Isoniazid, once daily, 300 mg, administered for 26 weeks. Drug: Pyrazinamide, once daily, dosage adjusted based on body weight: 1000 mg for < 55 kg, 1500 mg for ≥ 55-75 kg, and 2000 mg for >75 kg, administered for the first 8 weeks.
干预措施: Pyrazinamide (Drug)
结局指标
主要结局
TB-recurrence rate of spinal tuberculosis at 24 months after completion of treatment.
时间窗: 24 months after completion of treatment
The recurrence of spinal tuberculosis is defined by the reappearance of pain, with or without sinus formation, loosening or displacement of internal fixation on X-ray, and confirmed by postoperative CT or MRI showing increased local abscess, bone graft absorption, new sequestrum formation, or aggravated bone destruction.
The proportion of participants with grade 3 or more adverse events during study medication
时间窗: Throughout the study drug treatment period, about 36 months
次要结局
- TB-recurrence rate of spinal tuberculosis 12 months after completion of treatment(12 months after completion of treatment)
- The proportion of participants who are culture negative at eight weeks(At the end of 8 weeks of treatment)
- The proportion of discontinuation of assigned treatment for a reason other than microbiological ineligibility(Throughout the study period, an average of 1 year, up until the point of treatment discontinuation due to reasons other than microbiological failure)
- The incidence of adverse events(Throughout the study drug treatment period, about 36 months)
- The proportion of participants who have residual neurological dysfunction(Throughout the study drug treatment period, about 36 months)
- PK parameters of the anti-TB drugs(At the end of therapy, WEEK 52 for empirical long-course regimen, WEEK 26 for Short-course regimen)
- PD target attainment rate of the anti-TB drugs(At the end of therapy, WEEK 52 for empirical long-course regimen, WEEK 26 for Short-course regimen)
- Clinical cure at the end of therapy(At the end of therapy, WEEK 52 for empirical long-course regimen, WEEK 26 for Short-course regimen)
研究者
Wei Zhao
Head of department of clinical pharmacy and pharmacology
Shandong University