Efficacy, Security, Adherence, Tolerability and Cost Effectiveness of Latent TB Treatment in Patients With TB/DM2
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 396
- 试验地点
- 1
- 主要终点
- Efficacy of treatment with rifampicin compared to efficacy of treatment with isoniazid
研究概览
简要总结
Researchers will evaluate the efficacy, toxicity, adherence and cost effectiveness of treatment with isoniazid or rifampicin in patients with diabetes mellitus type two (DM2) and latent TB (LTB).
This is a collaborative study with participation from three national institutes (Instituto Nacional de Salud Pública (INSP), Instituto Nacional de Enfermedades Respiratorias (INER) and the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran (INCMNSZ)).
The study will take place in the VII sanitary jurisdiction of Orizaba and the INCMNSZ that has the necessary infrastructure and human resources. Researchers will evaluate 3000 patients with diabetes using a standardized questionnaire and a tuberculin skin test (TST) test. Eligible patients will be invited to participate and from those that agree to participate and sign a written informed consent we will obtain clinical, epidemiological, nutritional and metabolic information. Patients with altered liver function tests will be excluded.
详细描述
This study is a randomized control trial, with two parallel arms, fixed assignment, fixed sample size and in two study sites. Participants will be assigned 1:1 to receive one of the two treatment regimens: isoniazid for 6 months or rifampicin for 3 months. The assignment will be fixed because the covariates that predict the clinical outcome and the accumulated outcome of participants will not affect treatment assignment. In patients that the Michigan evaluation identifies as having neuropathic changes researchers will perform an electroneurography in order to identify the degree of neuropathy if any. This will be performed in the neurophysiology lab of the INCMNSZ. An independent comity will monitor adverse events.
Sample size It is necessary to include 193 participants, for each arm; this includes a 20% increase to compensate loss during follow up. This will provide a power equal or higher than 80% considering an alpha of 0.05 (.25 at two tails) in order to answer to each one of the following objectives.
Latent tuberculosis treatment with isoniazid is the gold standard and given its efficacy it would not be ethical to propose a placebo group. Researchers hypothesize that treatment with rifampicin will not be inferior in efficacy (measured using the response of biomarkers) and will be equivalent in toxicity to that observed with isoniazid treatment.
Subjects will be asked to attend on the 15th and 30th of the month and then once a month till the end of treatment. In case a patient does not assist, researchers will carry out a home visit.
Clinical, microbiological and metabolic evaluation
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Type 2 diabetes mellitus (DM2) diagnosed based on the National Official Norm
- •respiratory symptoms
- •Tuberculin Skin Test (TST) >10mm of induration
- •chest X ray without pleural, lung or mediastinal lesions
- •hemoglobin < 8 gm/dl
- •platelets > 60,000 per microliter
- •bilirubin < 2.5 mg/dl
- •Aspartate aminotransferase (AST) , Glutamic oxalacetic transaminases (SGOT) and alkaline phosphatase less than twice the normal value
- •negative pregnancy test
- •negative Human immunodeficiency virus infection test (HIV test)
- •signed written informed consent.
排除标准
- •Attending selected cites
- •Respiratory symptoms defined as cough with or without sputum for more than 2 weeks
- •Evidence or clinical suspicion of active tuberculosis (TB)
- •Current treatment with antituberculous drugs
- •History of having received more than one month's treatment for latent Tuberculosis (LTB) or antituberculous drugs
- •Hypersensitivity or intolerance to isoniazid or rifampicin
- •Active hepatopathy
- •Grade III or higher peripheral neuropathy
- •Chronic alcohol ingestion
- •Contacts of patients with isoniazid or rifampicin drug resistance
研究组 & 干预措施
Isoniazid
Diabetic patients with a positive TST of >10mm, will be randomly assigned to receive treatment with isoniazid 300mg Oral Tablet daily plus pyridoxine 50mg daily for six months
干预措施: Isoniazid 300 mg Oral Tablet (Drug)
Rifampin
Diabetic patients with a positive TST of >10mm, who wil be randomly assigned to receive treatment with rifampin 600mg Oral Tablets daily for three months
干预措施: Rifampin 600 mg Oral Tablet (Drug)
结局指标
主要结局
Efficacy of treatment with rifampicin compared to efficacy of treatment with isoniazid
时间窗: Up to 18 months
Researchers will measure with ELISA in vitro production of interferon gamma of peripheric mononuclear cels as a response to stimuli by RV0849 and RV1737 antigens. The cut of value is of \>100pg/ml.
Toxicity (neuropathy)
时间窗: Up to 6 months
Neurological alterations will be assessed using the Michigan questionnaire and in a subsample they will evaluate neuropathy using electroneurography.
Adherence
时间窗: Up to 6 months
Counting the number of administered pills, adequate adherence is more than 80% of administered pills.
Toxicity (liver function)
时间窗: Up to 6 months
Liver function tests
次要结局
未报告次要终点
研究者
Ma. de Lourdes Garcia Garcia
Director of prevention of infectious diseases
Instituto Nacional de Salud Publica, Mexico