Characterization of Tuberculosis Associated Lung Fibrosis and Respiratory Impairment, and Prevention Using Doxycycline in A Double Blind Randomized Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 200
- 试验地点
- 2
- 主要终点
- Efficacy of doxycycline as an anti-TB associated fibrosis agent
研究概览
简要总结
The goal of this clinical trial is to assess the efficacy(effectiveness) of doxycycline, a potent inhibitor of matrix metalloproteinase (lung collagenase) activity in prevention of Tuberculosis associated lung fibrosis and associated lung function decline among patients with drug sensitive advanced TB. The main question[s] it aims to answer are:
- Does doxycycline have a significant anti-fibrosis role when given as adjuvant therapy to TB patients with advanced pulmonary TB in a double blind randomized placebo controlled trial?
- How does long term respiratory function defer between patients who received adjuvant doxycycline aimed at prevention of TB associated lung fibrosis and those who received a placebo in a double blind randomized controlled trial?
Participants will be subjected to the following:
- Experimental arm: Doxycycline 100 mg once daily for 12 weeks administered concurrently with standard of care anti-TBs.
- Comparator arm: Placebo once daily for 12 weeks administered concurrently with standard of care anti-TBs.
详细描述
This will be a double-blind randomized block stratified clinical trial. Participants will be enrolled if they have advanced drug sensitive TB evidenced by infiltrates/lesions in at least 2 zones on a chest X-ray, among other inclusion criteria.
Participants will receive 100mg of doxycycline or matching placebo once a day for 12 weeks in addition to standard anti TB therapy.
Participants will undergo baseline high resolution CT scans to evaluate lung parenchyma involvement and repeat CT scans at 12 months to score TB associated fibrosis.
Lung function assessment with spirometry will be done at 6 and 12 months after enrolment to assess trends of lung function in the control and intervention study arms.
Profibrotic cytokines (TGFbeta) and Matrix metalloproteinases (1, 3 ,8,9) will be measured at baseline , 3 and 6 months after enrolment.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double blind study
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
- •Age of 18 - 65 years
- •Index PTB episode (sputum smear positive or GeneXpert positive with rifampicin susceptibility)
- •Baseline CXR showing infiltrates in at least 2 lung zones (≥30% lung involvement) meeting criteria for moderate/advanced PTB
- •HIV uninfected
- •Subjects willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
- •Able to give written informed consent.
排除标准
- •Pregnancy
- •Breastfeeding
- •Baseline serum creatinine or liver enzymes >2 times above upper limit of normal
- •Taking corticosteroids for ≥14 days or anti-TBs >7days
- •Prospects already enrolled in another clinical trial
- •Diabetic patients (most diabetics are on metformin or have history of metformin use. Metformin is postulated to have an anti-fibrosis role)
- •Patients with malignancy or on anticancer medication
- •Situation where a participant is taking a drug/medication known to interact with the trial drug.
- •Known allergies to doxycycline or other tetracyclines
- •Known autoimmune disease
- •Any factor felt to significantly increase risk of adverse event
研究组 & 干预措施
Intervention: Doxycycline
Oral doxycycline (100 mg) administered once daily for 12 weeks
干预措施: Doxycycline (Drug)
Control arm
Oral placebo (matching with doxycycline) will be administered once daily for 12 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
Efficacy of doxycycline as an anti-TB associated fibrosis agent
时间窗: 12 months
This will be estimated or analyzed using analysis of covariance method. The difference in the mean 'total HRCT fibrosis score' between the intervention and control study arms shall be compared at 12 months adjusting for the total scores measured at baseline. A linear regression model shall be fit on log transformed values of total HRCT scores for each individual.
Mean High resolution CT (HRCT) fibrosis scores
时间窗: 12 months
Quantified fibrosis scores (e.g. 0 - 25) will be derived from the CT interpretation tool, and recorded for each participant at baseline and 12 months' HRCT images, and compiled per treatment arm. Mean scores per study arm (intervention and control) will de determined for both baseline and 12 months' HRCT scans.
次要结局
- Lung function assessment(12 months)
- Correlation between the High-Resolution CT fibrosis score and lung function assessment(12 months)
- comparison of trends of cytokines (matrix metalloproteinases and TGF beta) between intervention and control arm(6 months)