An Open Label Randomized Controlled Clinical Trial Comparing a 24Week Oral Regimen Containing Moxifloxacin With a 24 Week Standard Drug Regimen for the Treatment of Smear-positive Pulmonary Tuberculosis in Patients Previously Treated for TB
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 197
- 试验地点
- 1
- 主要终点
- Sputum Culture Conversion Rates at Week 8 and Month 6 Post Tuberculosis Treatment Initiation
研究概览
简要总结
This is an open label randomized controlled clinical trial comparing two regimens for treatment of smear-positive pulmonary TB, among patients previously treated for TB. The primary objective is to determine if a moxifloxacin-containing regimen, substituting moxifloxacin for ethambutol, of 24 weeks duration is superior to a control regimen of 24 weeks duration in improving treatment outcomes in patients with recurrent TB and shortens the duration of TB treatment.
详细描述
Intervention Arm :12 months (6 months treatment + 12 months post treatment follow up) Control Arm :12 months (6 months treatment + 12 months post treatment follow up) Total sample size is 330.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults ≥ 18 years of age
- •Previous history of anti-TB chemotherapy
- •HIV status: HIV infected and uninfected patients are allowed in the study:
- •All patients must agree to HIV testing to confirm HIV status.
- •Patients already on ARVs will be allowed in the study provided that the ART regimen is not contraindicated with any of the study agents .
- •HIV infected patients at any CD4 count irrespective of ART commencement and duration will be included in the study
- •Smear positive or Gene Xpert positive pulmonary tuberculosis
- •Rifampicin susceptible as determined by Gene Xpert at screening. Gene Xpert will be used to determine rifampicin resistance, hence the study team will made aware of resistance within 48 hours and prior to study enrolment.
- •Karnofsky score greater than 70
- •Female candidates of reproductive potential must agree to use two reliable methods of contraception while on study: a barrier method of contraception (condoms or cervical cap) together with another reliable form of contraceptive (condoms with a spermicidal agent, a diaphragm or cervical cap with spermicide, an Intrauterine Device (IUD), or hormone-based contraceptive)
- •A negative pregnancy test
- •Laboratory parameters done at, or 14 days prior to, screening:
- •Haemoglobin level of at least 7.0 g/dL
- •Serum aspartate transaminase (AST) and alanine transaminase (ALT) activity less than 3 times the upper limit of normal
- •Serum total bilirubin level less than 2.5 times upper limit of normal
- •Creatinine clearance (CrCl) level greater than 60 mls/min
- •Platelet count of at least 50 x109cells/L
- •Serum potassium greater than 3.0 mmol/L
排除标准
- •Patients on a Nevirapine (NVP)-containing ART regimen at screening
- •Pregnant or breastfeeding
- •Received an antibiotic active against M. tuberculosis in the last 14 days (e.g. fluoroquinolones, macrolides, standard anti-tuberculosis drugs).
- •Patients with known M. tuberculosis resistance to any of the study drugs at screening
- •History of prolonged QT syndrome or current or planned therapy with quinidine, procainamide, amiodarone, sotalol, or ziprasidone during the intensive phase of tuberculosis treatment.
- •Known allergies or intolerance to any of the study drugs.
研究组 & 干预措施
Moxifloxacin
A Moxifloxacin-containing oral regimen of Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), Moxifloxacin (M), substituting Moxifloxacin for Ethambutol, daily for 24 weeks, see information below.
Intensive phase 7 days a week for 8 weeks Continuation phase - 7 days a week for 16 weeks
RH(150,75mg), Z (500mg), M (400mg) Dosage and number of tablets dispensed is dependent on participants weight band.
干预措施: moxifloxacin (Drug)
Ethambutol
An Ethambutol oral regimen of Isoniazid (H), Rifampicin(R), Pyrazinamide (Z), Ethambutol(E), daily for 24 weeks duration, substituting Ethambutol for Moxifloxacin.
Intensive phase 7 days a week for 8 weeks Continuation phase - 7 days a week for 16 weeks.See details below.
(150,75,400,275 mg) RHZE Dosage and number of tablets dispensed is dependent on participants weight band.
干预措施: moxifloxacin (Drug)
结局指标
主要结局
Sputum Culture Conversion Rates at Week 8 and Month 6 Post Tuberculosis Treatment Initiation
时间窗: 24 weeks
The proportion of patients with negative sputum cultures at the end of the intensive phase (8 weeks) and the proportion of patients with negative sputum cultures at 6 months were compared between the two study arms. All participants with sputum culture results at week 8 and month 6 were included in the analysis.
次要结局
- Number of Participants With Adverse Events and 8-week Culture Conversion Rates Among HIV-infected Patients vs. HIV-uninfected Patients(up to 2 years for adverse events and 8 weeks for culture conversion rates)
- Proportion of Patients With Unfavourable Outcomes or Tuberculosis Recurrence in the Moxifloxacin and Control Arm.(up to 2 years)
- Time to Culture-conversion of the Moxifloxacin Regimen and the Ethambutol Regimen(Up to 2 years)
- Proportion of Patients With Any Grade 3 or 4 Adverse Reactions in the Two Study Arms(Up to 2 years)
研究者
Dr Nesri Padayatchi
Principle Investigator
Centre for the AIDS Programme of Research in South Africa