Personalization of AntiTB Treatment: Evaluation of Pharmacological Determinants of Treatment Response
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 257
- 试验地点
- 1
- 主要终点
- Correlation between AUC of RHZE and TTP
研究概览
简要总结
The aim of the study is to investigate the possible correlation of plasma drug concentrations with Time To Positivity (TTP) in liquid culture in patients with active pulmonary multi sensitive TB in the first two weeks of treatment. Secondary aims are: the correlation between plasma drug concentrations and hepato/neuro toxicity; the impact of different allelic variants on PK data, toxicity and TTP in liquid culture; the feasibility of using dried blood/plasma spots to measure plasma concentrations of anti-TB drugs and determine genetic polymorphisms.
详细描述
A longitudinal observational multicentred study will be conducted in patients with diagnosis of active pulmonary TB.
The following variables will be recorded:
- demographic variables: age, gender, ethnicity, SNPs for NAT2, SLCO1B1, ABCB1 and VDR;
- clinical variables: weight, height, renal function tests, liver function tests, vitamin D (25-OH vitamin D) level, albuminemia, serology for HIV, HCV, presence of comorbidities (e.g. diabetes mellitus), visual acuity test, presence of neuropathic symptoms;
- microbiological variables: phenotypic and genotypic drug sensitivity test results, sputum Mycobacterium tuberculosis DNA (PCR), microscopy, culture, Time To Positivity (TTP) in liquid culture, IGRA test (if performed), history of previous treatments, location of pulmonary lesions, presence of extra-pulmonary locations;
- therapeutic variables: start/end of treatment, treatment interruptions, dose mg/kg, route of administration.
The patients will received standard antitubercular drugs according to international guidelines (RIF 10 mg/kg, INH 5 mg/kg maximum dose 300 mg, ETB 15-20 mg/kg, PZA 25 mg/kg maximum dose 2000 mg) in fasten condition, once daily.
To measure plasma concentrations four blood samples (Lithium heparin 7 ml tubes) will be collected at 0, 2, 4 and 6 hours post dose. This analysis will be performed at 7 and 14 days after the beginning of anti-TB treatment.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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
- •signed informed consent
- •age >=18 years;
- •pulmonary tuberculosis defined by positive sputum microscopy (waiting for culture confirmation)
- •sensitivity to first-line anti-TB drugs;
- •normal liver and renal function.
排除标准
- •severe malnutrition;
- •HIV infection
结局指标
主要结局
Correlation between AUC of RHZE and TTP
时间窗: 2 weeks from start of treatment
Investigate the correlation of plasma drug concentrations (Rifampicin, Isoniazid, Ethambutol and Pyrazinamide, HRZE) with the change in Time To Positivity (TTP) in liquid culture in patients with active pulmonary TB between the baseline and the second week of treatment.
次要结局
- Correlation between AUC of RHZE and toxicity(1 week and 2 weeks from start of treatment)
- Assess the consistency of results using of DPS for measuring the plasma drug concentrations(1 week and 2 weeks from start of treatment)
- Correlate AUC of RHZE with antiTB response(6 months after end of treatment)
- Correlate PG with antiTB response(6 months after end of treatment)
- Correlation between PG and AUC of RHZE(1 week and 2 weeks from start of treatment)
研究者
Ilaria Motta
Principal Investigator
University of Turin, Italy