Combined Dry Powder Tobramycin and Nebulized Colistin Inhalation in CF Patients
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 26
- 主要终点
- Amount of P. aeruginosa in sputum
研究概览
简要总结
To assess whether the inhalative combination of Tobramycin/Colistin is more effective in reducing Pseudomonas colony forming units (CFUs) and improvement of lung function than Colistin in mono-therapy.
详细描述
Cystic fibrosis (CF), the most common autosomal recessive disorder in Western countries, is caused by mutations of the cystic fibrosis transmembrane conductance regulator molecule (CFTR) and affects approximately 40.000 patients in Europe. The majority of CF patients develop chronic pulmonary infections with Pseudomonas aeruginosa. These are normally treated with single antibiotics, administered orally, intravenously or inhalatively. Once the infection becomes chronic, eradication of the pathogen is not any more possible due to biofilm formation of the pathogen and increasing resistance. However, inhalative antibiotic combination therapy might be more efficient than single antibiotic therapy in chronically infected CF patients. This notion is supported by previous in vitro and animal studies using Tobramycin/Colistin combination therapy. Importantly, a pilot study in five CF patients who inhaled consecutively Colistin and Tobramycin solutions for 4 week, revealed a decrease of log10 2.52 ± 2.5 cfu of P. aeruginosa in sputum specimens during the course of the treatment compared to baseline values (p=0.027). The treatment was shown to be safe and well tolerated. However, forced expiratory volume in 1 sec (FEV1) did not differ significantly.
Taking advantage of the new development of dry powder inhalation (DPI) antibiotics, specifically TOBI© Podhaler, a larger randomised trial has been performed in which the combined TOBI© Podhaler and Colistin treatment is compared to the monotherapy with Colistin.
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Cystic Fibrosis is verified;
- •Patient is 12 years or older;
- •FEV1 is higher than 25% and lower than 100%;
- •The patients' lung is colonised with P. aeruginosa chronically (≥6 months);
- •P. aeruginosa must be sensitive for Tobramycin or Colistin;
- •Pretreated with Colistin >2 months;
- •Last i.v. antibiotic treatment ≥2 weeks;
- •Informed consent is given by patients/legal representatives
排除标准
- •Clinical deterioration is present (exacerbation symptoms);
- •Last Tobramycin inhalation treatment ≤ 2 weeks;
- •Renal dysfunction (creatinine <1.5 fold of normal, glomerular filtration rate (GFR) <80%) at baseline
- •auditoria or vestibular dysfunction, hearing loss
- •Intolerances against Tobramycin, Colistin or Polymyxin B
- •Myasthenia gravis
- •Pregnancy and nursing
研究组 & 干预措施
Tobramycin powder / Colistin
TOBI®Podhaler 2 x 112 mg daily for 2 x 28 days (on/off); and Colistin solution 2 x daily 1 Mega continuously for 112 days
干预措施: Tobramycin Powder (Drug)
Tobramycin powder / Colistin
TOBI®Podhaler 2 x 112 mg daily for 2 x 28 days (on/off); and Colistin solution 2 x daily 1 Mega continuously for 112 days
干预措施: Colistin (Drug)
Colistin
Colistin solution 2 x daily 1 Mega continuously for at least 30 days
干预措施: Colistin (Drug)
结局指标
主要结局
Amount of P. aeruginosa in sputum
时间窗: 30 days
The primary endpoint will be the difference of P. aeruginosa cfu/ml in sputum with combined therapy with Tobramycin/Colistin compared to colistin mono-therapy. The analysis will be adjusted for baseline values of each cycle and parametric (paired t-Test) or non-parametric (sign test) methods will be used as appropriate.
次要结局
- Course of forced vital capacity (FVC) absolute amount(112 days)
- Course of leukocyte amount in sputum(112 days)
- Exacerbation(112 days)
- Course of FVC relative amount(112 days)
- Course of proinflammatory cytokine IL1ß amount(112 days)
- Course of DNA amount in sputum(112 days)
- Antibiotics(112 days)
- Course of P.aeruginosa amount in sputum(112 days)
- Course of FEV1 absolute amount(112 days)
- Course of FEV1 relative amount(112 days)
- Course of proinflammatory cytokine IL6 amount(112 days)
- Course of MEF25-75 relative amount(112 days)
- Course of proinflammatory cytokine IL8 amount(112 days)
- Course of antiinflammatory cytokine IL10 amount(112 days)
- Course of proinflammatory cytokine TNFa amount(112 days)
- Course of proinflammatory cytokine GM-CSF amount(112 days)
- Course of MEF25-75 absolute amount(112 days)