A Prospective, Randomized Pilot Study of the Immunomodulatory Effects of Azithromycin in Adults With Pulmonary Tuberculosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Systemic inflammation
研究概览
简要总结
Rationale:
Treatment in tuberculosis (TB) is focused on eradication of the bacterial infection, however, after treatment approximately half of patients are left with a significant and permanent respiratory impairment. Adjunctive host-directed therapies are being investigated to modulate host immune responses to target mycobacterium tuberculosis (Mtb) infection and/or reduce excessive inflammation, prevent pathological tissue damage, preserve lung function and enhance effectiveness of standard drug therapy, while nonetheless eliminating Mtb. Macrolide antibiotics have previously been used in the treatment of multidrug-resistant TB. In addition to their antibiotic effects, macrolides have also been recognized to induce anti-inflammatory and immunomodulatory effects in other lung diseases.
Objective:
To investigate the immunomodulatory effects of azithromycin in tuberculosis patients receiving standard therapy (isoniazid, rifampicin, pyrazinamide, ethambutol (HRZE))
Study design:
A prospective, randomized open label intervention trial to investigate the immunomodulatory effects of azithromycin
Study population: 24
Intervention: azithromycin 250 mg once daily or standard of care (control)
Main study parameters/endpoints:
- To assess whether azithromycin enhances resolution of systemic inflammation in patients with drug susceptible pulmonary TB receiving standard treatment.
- To assess whether azithromycin on top of standard treatment in patients with drug susceptible pulmonary TB reduces airway inflammation and reduces tissue degradation and remodeling
- To investigate whether these effects are associated within shortening of the time to sputum conversion.
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 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinical diagnosis of drug sensitive pulmonary tuberculosis (molecular test; identification Mtb complex; absence of resistance genes such as rpob, inha, katg)
- •Written informed consent
排除标准
- •Patient reported previous history of treatment for tuberculosis
- •Patients younger than 18 years
- •Pregnancy or breast feeding
- •Patients with hypersensitivity to macrolide antibiotics
- •Treatment with any macrolide in the previous month
- •Treatment with any tetracycline in the previous month
- •Treatment with any inhaled or oral corticosteroid in the previous month
- •Concomitant treatment with analgesic (NSAIDs)/immunosuppressant drugs (except paracetamol).
- •Treatment with digoxin
- •Patients with gastrointestinal complaints, like diarrhea and vomiting (≥grade 2, observed)
- •Other known respiratory diseases, including bronchiectasis, pulmonary fibrosis, pulmonary vascular disease or lung cancer
- •HIV-1 infection or AIDS
- •Impaired liver function (Child-Pugh score C)
- •Patients with a known QTc ≥500 ms. An electrocardiogram (ECG) will be recorded.
- •Inability to spontaneously produce sputum upon diagnosis
研究组 & 干预措施
Azithromycin arm
Patients in this arm will be treated with azithromycin 250 mg once daily on top of standard HRZE treatment.
干预措施: Azithromycin 250 mg (Drug)
结局指标
主要结局
Systemic inflammation
时间窗: Before randomization, day 7 and day 28
Changes in serum inflammatory markers
次要结局
- Pulmonary inflammation(Before randomization and day 28)
- Pulmonary tissue degradation(Before randomization, day 7 and day 28)
- Pulmonary tissue remodeling(Before randomization, day 7 and day 28)
研究者
Jan-Willem C Alffenaar
Principal Investigator, PharmD, PhD
University Medical Center Groningen