Bronchiectasis Adult, Pseudomonas Infections
Conditions
Keywords
bronchiectasis, Pseudomonas aeruginosa, tobramycin, nebulization, bacterial load, quality of life
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.
Interventions
Tobramycin will be nebulized (300mg twice daily) with an ultrasonic nebulizer. A total of two 28-day on-and-off cycles will be scheduled.
OTHERusual care
ambroxool (30mg thrice daily), or N-acetylcysteine (0.2g thrice daily) plus chest physiotherapy (5 min, once daily)
Natural saline will be nebulized (5ml twice daily) with an ultrasonic nebulizer. A total of two 28-day on-and-off cycles will be scheduled.
Sponsors
Guangzhou Institute of Respiratory Disease
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
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.
Intervention model description
Patients will be randomized into the treatment group and control group. No cross-over of the study group will be made.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| The time to the first bronchiectasis exacerbation since randomization | 4 months | The time to the first bronchiectasis exacerbation since randomization |
| 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) |
| 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. |
| The frequency of bronchiectasis exacerbation since randomization | 4 months | The frequency of bronchiectasis exacerbation since randomization |
Countries
China
Contacts
Primary ContactNan-shan Zhong, MD
Backup ContactWei-jie Guan, PhD
Outcome results
None listed