Supplementary Oral Azithromycin in Treatment of Intermittent Pseudomonas Aeruginosa Colonization in CF-patients With Inhaled Colistin and Oral Ciprofloxacin; Postponing Next Isolate of Pseudomonas and Prevention of Chronic Infection. A Prospective, Double-blinded, Placebo-controlled Scandinavian Multi-centre Study.
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 45
- 试验地点
- 8
- 主要终点
- Time to next airway-colonization (re-colonization) with Pseudomonas aeruginosa
研究概览
简要总结
In patients with Cystic Fibrosis, recurrent airway infection caused by Pseudomonas aeruginosa ultimately leads to chronic airway infection. The purpose of this study is to determine whether supplementary low-dose azithromycin to standard inhaled colistin and oral ciprofloxacin in the treatment of intermittent pseudomonas airway-infection can postpone the next episode of intermittent pseudomonas airway-infection and prevent development of chronic airway-infection.
详细描述
Cystic Fibrosis is the most common genetic, inherited, deadly disease in caucasians. The disease is characterized by recurrent airway-infections caused by Pseudomonas aeruginosa, ultimately leading to chronic airway-infection, which is the main cause of the increased morbidity and mortality seen in this disease.
P. aeruginosa has the ability to change to mucoid phenotype - producing alginate and growing in biofilm, which protects the microorganisms from antibiotics and leukocytes. The change in phenotype is seen as chronic infection is established and eradication becomes impossible. Treatment with long-term, low-dose azithromycin in chronically infected CF-patients can improve the clinical condition of the patients. The exact mechanism for this is not known, but is possibly a combination of anti-inflammatory effects and the ability of azithromycin to inhibit alginate-production. Inhibition of biofilm-formation leaves the bacteria more susceptible to the actions of antibiotics and leukocytes.
Prior to establishment of chronic infection, recurrent, intermittent colonization of the airways with non-mucoid P. aeruginosa is seen. Intermittent infections can be treated using a combination of antibiotics, thereby postponing the next episode of airway-infection with P. aeruginosa.
The purpose of this study is to clarify wether supplementary azithromycin in the treatment of intermittent pseudomonas-infection in CF-patients can lead to further postponement of next pseudomonas-colonization and maybe prevent development of chronic infection. This is done in a randomised, double-blinded, placebo-controlled multicentre study.
2 treatments will be compared:
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
- Double (Participant, Care Provider)
入排标准
- 年龄范围
- 1 Year 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of Cystic Fibrosis based on genotype and/or positive sweat-test
- •Written informed consent based on written and spoken information
- •No chronic airway-infections with Gram-negative bacteria
- •Fertile, sexually active women must use contraception (p-pills, IUD or other methods with a similar Pearl-index) when participating in the study
排除标准
- •P. aeruginosa in airway secretions obtained less than 3 months prior to inclusion
- •Chronic infection of the airways caused by Gram-negative bacteria (Burkholderia species, Achromobacter xylosoxidans, Pandorea apista or Stenotrophomonas maltophilia)
- •Chronic infection of the airways caused by P. aeruginosa (chronic infection is defined by continuing growth of the microorganism for 6 months and/or an increase in specific, precipitating antibodies to a level of at least 2)
- •Previous infection with a strain of P. aeruginosa resistant to ciprofloxacin or colistin
- •Previous participation in a pseudomonas-vaccination-study
- •Patients younger than 1 year
- •Pregnant or lactating women, or sexually active women unwilling to use safe contraception (p-pills, IUD or method with similar Pearl-index) when participating in the study
- •Severe insufficiency of the liver or kidneys as judged by the local investigator
研究组 & 干预措施
C
Stratification group: Age >/= 8 years, CF siblings at home.
干预措施: Azithromycin or placebo tablets (Drug)
A
Stratification group: Age under 8 years, no CF siblings at home.
干预措施: Study medication, azithromycin or placebo (Drug)
B
Stratification group: Age >/= 8 years, no CF siblings at home.
干预措施: Azithromycin or placebo tablets (Drug)
结局指标
主要结局
Time to next airway-colonization (re-colonization) with Pseudomonas aeruginosa
时间窗: up to 5 years
次要结局
- Clinical condition of the patients (height, weight and lung function)(up to 5 years)
- Bacteriological examination of Pseudomonas aeruginosa (phenotype, resistance)(5 years)
- Genotyping of Pseudomonas aeruginosa using Pulsed Field Gel Electrophoresis (re-infection caused by identical or new strain)(5 years)
- Specific, precipitating pseudomonas-antibodies (establishment of chronic infection)(5 years)
研究者
Christine Hansen
Medical doctor
Rigshospitalet, Denmark