Tobramycin in Bronchiectasis Colonized With Pseudmonas Aeruginosa
- Conditions
- Bronchiectasis AdultPseudomonas Infections
- Interventions
- Registration Number
- NCT03715322
- Lead Sponsor
- Guangzhou Institute of Respiratory Disease
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 350
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description tobramycin inhalation usual care 300mg tobramycin dissolved in 5ml saline will be nebulized with an ultrasonic nebulizer within 15-20 minutes. natural saline inhalation usual care 5ml saline will be nebulized with an ultrasonic nebulizer within 15-20 minutes. natural saline inhalation Natural saline inhalation 5ml saline will be nebulized with an ultrasonic nebulizer within 15-20 minutes. usual care Tobramycin Inhalant Product ambroxool (30mg thrice daily), or N-acetylcysteine (0.2g thrice daily) plus chest physiotherapy (5 min, once daily) usual care Natural saline inhalation ambroxool (30mg thrice daily), or N-acetylcysteine (0.2g thrice daily) plus chest physiotherapy (5 min, once daily) tobramycin inhalation Tobramycin Inhalant Product 300mg tobramycin dissolved in 5ml saline will be nebulized with an ultrasonic nebulizer within 15-20 minutes.
- Primary Outcome Measures
Name Time Method Changes in sputum load of Pseudomonas aeruginosa at day 29 compared with baseline 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 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.
- Secondary Outcome Measures
Name Time Method The frequency of bronchiectasis exacerbation since randomization 4 months The frequency of bronchiectasis exacerbation since randomization
The rate of isolation of Pseudomonas aeruginosa at day 85 85 days The rate of isolation of Pseudomonas aeruginosa at day 85
Changes in the load of Pseudomonas aeruginosa at day 85 compared with baseline 85 days Changes in the load of Pseudomonas aeruginosa at day 85 compared with baseline
The time to the first bronchiectasis exacerbation since randomization 4 months The time to the first bronchiectasis exacerbation since randomization
Changes in FEV1 pred% at days 29, 57 and 85 compared with baseline 85 days Changes in the predicted % of forced expiratory volume in one second at days 29, 57 and 85 compared with baseline
Changes in 24-hour sputum volume 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
Changes in sputum purulence at days 29, 57 and 85 compared with baseline 85 days Changes in sputum purulence at days 29, 57 and 85 compared with baseline
Changes in Quality of Life in Bronchiectasis-Respiratory Symptom Score at day 85 compared with baseline 85 days Changes in QoL-B-RSS at day 85 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.
Changes in Bronchiectasis Health Questionnaire Sore at day 29 and 85 compared with baseline 85 days Changes in BHQ Sore at day 29 and 85 compared with baseline. Theb BHQ contains 10 items, with higher scores indicating better quality of life. The total score was calculated as the weighted summation of the scores for the 10 individual items.
Peak and trough concentration of tobramycin at day 1 and 28 post-treatment 29 days Peak and trough concentration of tobramycin at day 1 and 28 post-treatment
Changes in overall visual analogue scale at days 29 and 85 compared with baseline 85 days Changes in overall VAS at days 29 and 85 compared with baseline. The VAS ranged from 0 to 10, with higher scores indicating poorer status. No summation of the score was made.
Changes in the minimal inhibitory concentration of Pseudomonas aeruginosa at days 29 and 85 compared with baseline 85 days Changes in the MIC of Pseudomonas aeruginosa at days 29 and 85 compared with baseline (assessed with dilution methods for the sputum culture samples)
Trial Locations
- Locations (1)
The First Affiliated Hospital of Guangzhou Medical University
🇨🇳Guangzhou, Guangdong, China