A 14 Day Early Bactericidal Activity Study of Nitazoxanide for the Treatment of Tuberculosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- time to positivity (TTP)
研究概览
简要总结
This research is being done to determine if Nitazoxanide (NTZ) will cause a significant decrease in the number of M. tuberculosis bacteria in sputum after 14 days of treatment. The study is being conducted at the GHESKIO Centers in Port au Prince Haiti
详细描述
This is a prospective randomized two-arm 14-day, early bactericidal activity study in treatment-naive, drug-susceptible patients with uncomplicated pulmonary tuberculosis (TB). The study will be conducted at the GHESKIO Centers in Port au Prince Haiti. Twenty patients will be randomized to receive NTZ 1 gram orally twice daily for 14 days. Ten patients will be randomized as positive controls to receive standard 4 drug tuberculosis therapy with isoniazid (H), rifampin (R), ethambutol (E), and pyrazinamide (PZA). Patients' sputum will be collected before and then every two days during 14 days of treatment, and the primary endpoint will be the change in the number of M. tuberculosis in patients' sputum. Our primary hypothesis is that NTZ will result in a significant decrease in the number of M. tuberculosis in sputum during14 days of treatment. The number of M. tuberculosis will be quantified by the time to positive (TTP) signal in hours in an automated liquid media culture system (BACTEC MGIT 960, Becton Dickinson).
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
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women ages 18 - 65
- •Diagnosed with pulmonary tuberculosis via: sputum-microscopy smear-positive (2+ or 3+) within 14 days plus Sputum GeneXpert positive within 14 days plus Chest radiograph consistent with M. tuberculosis within 14 days
- •TB treatment naïve at time of enrollment
- •Bodyweight > 40kg
- •Negative HIV test within 30 days
- •Able to complete activities of daily living (ADLs)
- •All participants must agree not to participate in a conception process (i.e. active attempt to become pregnant or to impregnate, donate sperm, in vitro fertilization)
- •All female participants must agree to use barrier methods such as condoms as well as hormonal contraception for dual prophylaxis.
- •Able to give informed consent and demonstrate understanding of this study and willingness to participate in this study
- •Willing to be hospitalized for 2 weeks
排除标准
- •Pregnancy
- •Evidence of complications of M. tuberculosis such as hemoptysis or shortness of breath
- •Extrapulmonary manifestations of M. tuberculosis
- •History of prior active tuberculosis
- •Evidence of rifampin resistance via GeneXpert
- •Previous diagnosis of diabetes or suggestion of impaired glucose metabolism via random plasma glucose
- •Previous diagnosis of HIV by any rapid HIV test or by ELISA
- •Any of the following lab abnormalities: Creatinine > 1.5 times the ULN; Random glucose > 2 times the ULN; ALT, AST, or alkaline phosphatase > 2 times the ULN; Hemoglobin < 7.5 g/dL
- •Any participant currently taking antimycobacterial therapy or within the past 30 days
- •Any concomitant illness that could compromise patient safety in this trial such as renal failure, chronic liver disease or alcoholic dependency
- •Enrolled in another clinical trial
研究组 & 干预措施
Nitazoxanide
Participants with drug-sensitive tuberculous randomized to the NTZ arm will receive nitazoxanide 1000 mg po twice daily for 14 days. After this time point, participants will be switched to WHO standard tuberculosis therapy with isoniazid, rifampin, pyrazinamide and ethambutol.
干预措施: Nitazoxanide (Drug)
Control
Participants with drug-sensitive tuberculosis randomized to the standard therapy arm will receive WHO standard tuberculosis therapy involving isoniazid 300 mg po daily, rifampin 600 mg po daily, pyrazinamide 25 mg/kg po daily and ethambutol 15 mg/kg po daily.
干预措施: Control (Other)
结局指标
主要结局
time to positivity (TTP)
时间窗: first 14 days of anti-tuberculosis therapy
To assess the change in time in hours to positive (TTP) signal in an automated liquid media culture system (BACTEC MGIT 960, Becton Dickinson) in participants receiving NTZ over 14 days
次要结局
- Number of participants with treatment-related adverse events as determined by DAIDS toxicity tables(first 14 days of anti-tuberculosis therapy)
- Maximum plasma concentration of NTZ(first 14 days of anti-tuberculosis therapy)
- Most probable number of M tuberculosis in 1 ml of sputum(first 14 days of anti-tuberculosis therapy)
- First-line drug susceptibility (DST) of Mycobacterium tuberculosis via Mycobacterial Growth Indicator System (MGIT)(first 14 days of anti-tuberculosis therapy)
- Quantification of change in urine metabolites and correlation with change in TTP(first 14 days of anti-tuberculosis therapy)
- Minimum plasma concentration of NTZ(first 14 days of anti-tuberculosis therapy)
- Area under the curve of NTZ metabolites(first 14 days of anti-tuberculosis therapy)
- Sputum concentration of NTZ(first 14 days of anti-tuberculosis therapy)
- Change in Minimum inhibitory concentration (MIC) of NTZ against Tuberculosis over 14 days(first 14 days of anti-tuberculosis therapy)
- Change in phylogeny of bacteria determined by sequencing of amplified 16S ribosomal DNA and/or metagenomic sequencing of bacterial DNA(first 14 days of anti-tuberculosis therapy)
- Transcriptional signature of treatment response using whole blood transcriptional profiles(first 14 days of anti-tuberculosis therapy)