Efficacy and Safety of Inhaled Tobramycin on Bronchiectasis Colonized With Pseudomonas Aeruginosa: A Randomized, Double-blind, Parallel-group Multicenter Trial
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 350
- 试验地点
- 1
- 主要终点
- Changes in sputum load of Pseudomonas aeruginosa at day 29 compared with baseline
研究概览
简要总结
This is a phase 3 study. Patients will be enrolled from 14 medical centers in mainland China. Eligible patients will be randomly allocated to treatment group (tobramycin nebulization, 300mg bid) and control group (natural saline nebulization, 5ml bid). A total of two 28-day on-and-off cycles will be scheduled. Both tobramycin solution and natural saline and the nebulizer will be solely provided by the sponsor.
详细描述
This is a phase 3 study. All bronchiectasis patients will be enrolled from 14 medical centers located in different geographic regions of mainland China. After a three-week screening period, On the basis of usual care [ambroxool (30mg thrice daily) or N-acetylcysteine (0.2g thrice daily) and chest physiotherapy (5 min, once daily)], eligible patients will be randomly allocated to treatment group (tobramycin nebulization, 300mg bid, delivered via an ultrasonic nebulizer) and control group (natural saline nebulization, 5ml bid, delivered via an ultrasonic nebulizer). A total of two 28-day on-and-off cycles will be scheduled. At the end of each on-and-off cycle, sputum culture and other clinical assessments will be performed.
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, Investigator)
盲法说明
Both the investigators and the participants will be masked to the study allocation. The randonmization codes will be generated by a blinded medical statistician with the use of computerized program. Randomization will be achieved based on the permuted block design.
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
- •Aged 18 to 75 years, had a history of chronic cough and sputum production, had physician-diagnosed bronchiectasis based on high-resolution chest computed tomography (effective within 12 months)
- •Remaining clinically stable (no significant changes in respiratory symptoms and free from upper respiratory tract infection or bronchiectasis exacerbations for 4 weeks)
- •Sputum culture positive to Pseudomonas aeruginosa at screening
- •Forced expiratory volume in one second > 30% predicted and < 80% predicted
- •Could tolerate to nebulization
- •At least one bronchiectasis exacerbation within the past two years
- •Can correctly nebulize the study medications and fill in the diary cards following instruction of the investigators
排除标准
- •Had a knwon history of allergy to tobramycin
- •Had concomitant asthma, allergic bronchopulmonary aspergillosis, active tuberculosis, or active infection with non-tuyberculous mycobacteria that warranted regular anti-mycobacterial treatment
- •Had moderate or major haemoptysis within 6 months
- •Had concomitant severe cardiovascular diseases or haematopoietic diseases (congestive heart failure, clinically significant coronary heart disease, myocardial infarction or stroke, clinically arrythmia, known anurysm of the aorta, uncontroll hypertension (systolic blood pressure > 160mmHg or diastolic pressure >100mmHg at two consecutive time points)
- •Concomitant severe psychiatric disorders
- •Uncontrolled diabetes mellitus or fasting blood glucose >10mmol/L
- •Active peptic or duodenal ulcer
- •Moderate-to-severe gastroesophageal reflux diseases
- •Malignancy
- •Severe myasthenia gravis or Parkinson's disease
- •Major abnormality of hepatic or renal function [ALT or AST >2-fold of the normal upper limit, creatinine > 1.5-fold- greater than the normal upper limit (excluding ALT > 1.5-fold greater than normal upper limit in patients with chronic stable hepatitis)]; concomitant infection with HBV and HCV;
- •Hearing loss or clinically significant tinittus
- •Use of inhaled or systemic antibiotics within 4 weeks prior to enrollment
- •Needing oral or intravenous corticosteroids, or needing systemic corticosteroids within 30 days prior to enrollment
- •Needing oral or intravenous anti-cholinergic medications, or needing systemic anti-cholinergic medications within 30 days prior to enrollment
- •Needing long-term non-invasive mechanical ventilation or oxygen therapy (> 10 hrs daily) due to chronic respiratory failure
- •Pregnancy or lactation
- •Failure to understand or cooperate with the trial procedures
- •Participation in other clinical trials within 3 months
研究组 & 干预措施
tobramycin inhalation
300mg tobramycin dissolved in 5ml saline will be nebulized with an ultrasonic nebulizer within 15-20 minutes.
干预措施: Tobramycin Inhalant Product (Drug)
tobramycin inhalation
300mg tobramycin dissolved in 5ml saline will be nebulized with an ultrasonic nebulizer within 15-20 minutes.
干预措施: usual care (Other)
natural saline inhalation
5ml saline will be nebulized with an ultrasonic nebulizer within 15-20 minutes.
干预措施: usual care (Other)
natural saline inhalation
5ml saline will be nebulized with an ultrasonic nebulizer within 15-20 minutes.
干预措施: Natural saline inhalation (Drug)
usual care
ambroxool (30mg thrice daily), or N-acetylcysteine (0.2g thrice daily) plus chest physiotherapy (5 min, once daily)
干预措施: Tobramycin Inhalant Product (Drug)
usual care
ambroxool (30mg thrice daily), or N-acetylcysteine (0.2g thrice daily) plus chest physiotherapy (5 min, once daily)
干预措施: Natural saline inhalation (Drug)
结局指标
主要结局
Changes in sputum load of Pseudomonas aeruginosa at day 29 compared with baseline
时间窗: 29 days
Changes in sputum load of Pseudomonas aeruginosa at day 29 compared with baseline
Changes in Quality of Life in Bronchiectasis-Respiratory Symptom Score at day 29 compared with baseline
时间窗: 29 days
Changes in QoL-B-RSS at day 29 compared with baseline. The respiratory symptom domain contains 9 items describing patient's self assessment of her/his respiratory symptoms that affect the daily life. The total score for this domain is 100, with higher scores indicating better quality of life. No summation was made for the total score.
次要结局
- The time to the first bronchiectasis exacerbation since randomization(4 months)
- The frequency of bronchiectasis exacerbation since randomization(4 months)
- The rate of isolation of Pseudomonas aeruginosa at day 85(85 days)
- Changes in the load of Pseudomonas aeruginosa at day 85 compared with baseline(85 days)
- Changes in FEV1 pred% at days 29, 57 and 85 compared with baseline(85 days)
- Changes in 24-hour sputum volume at days 29, 57 and 85 compared with baseline(85 days)
- Changes in sputum purulence at days 29, 57 and 85 compared with baseline(85 days)
- Changes in Quality of Life in Bronchiectasis-Respiratory Symptom Score at day 85 compared with baseline(85 days)
- Changes in Bronchiectasis Health Questionnaire Sore at day 29 and 85 compared with baseline(85 days)
- Peak and trough concentration of tobramycin at day 1 and 28 post-treatment(29 days)
- Changes in overall visual analogue scale at days 29 and 85 compared with baseline(85 days)
- Changes in the minimal inhibitory concentration of Pseudomonas aeruginosa at days 29 and 85 compared with baseline(85 days)
研究者
Weijie Guan
Associated professor; principal investigator (respiratory medicine)
Guangzhou Institute of Respiratory Disease