Inhaled Nebulized Tobramycin in Non-cystic Fibrosis Bronchiectasis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effect of tobramycin inhalation solution (TIS) once daily compared tot placebo in patients with non-CF bronchiectasis. The primary endpoint is a reduction of exacerbations of the disease during the treatment period. Next to this parameter the investigators expect to show a significant beneficial effect on lung function parameters, QoL, bacterial load of pathogens in sputum and tobramycin resistance.

Detailed Description
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See uploaded study protocol

Official Title
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Long-term Inhaled Nebulized Tobramycin in Patients With Non-cystic Fibrosis Bronchiectasis. A Randomized Placebo Controlled Trial. The BATTLE Study Bronchiectasis And Tobramycin SoluTion InhaLation ThErapy.

Conditions
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Non-CF Bronchiectasis

Intervention / Treatment
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* Drug: tobramycin inhalation solution
* Drug: Saline 0.9% inhalation solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years The presence of chronic respiratory symptoms such as cough, dyspnoea, expectoration of sputum Confirmed non-CF bronchiectasis by (HR)CT Documented history of at least 2 pulmonary exacerbations treated with courses of antibiotics within 12 months before inclusion. No course of antibiotics or maintenance antibiotics (except for macrolides) 1 month prior to the start of the study. Minimal one documented sputum or BAL-fluid culture with gram-negative bacteria or S.aureus within 12 months. Growth of protocol defined pathogens in sputum at screening visit sensitive to tobramycin Tolerance of inhaled tobramycin Exclusion Criteria: Any exacerbation within the month prior to the start of the study Diagnosis of cystic fibrosis Active allergic bronchopulmonary aspergillosis (ABPA) Any oral, IV or inhaled antibiotics (except for macrolides) within 1 month prior to the start of the study Any IV or IM corticosteroids or change in oral corticosteroids (> 10 mg) within 1 month prior to the start of the study Any change/start treatment regimens macrolides, hypertonic saline, inhaled mannitol or other mucolytics, corticosteroids within 1 month prior to the start of the study Change in physiotherapy technique or schedule within 1 month prior to the start of the study Severe immunosuppression or active malignancy Active tuberculosis Chronic renal insufficiency (eGFR < 30 ml/min), use of loop diuretics Have received an investigational drug or device within 1 month prior to the start of the study Serious or active medical or psychiatric illness Pregnancy and child bearing History of poor cooperation or non-compliance Unable to use nebulizers Allergic for tobramycin

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: . In present study the value of maintenance TIS will be investigated in patients with non-CF bronchiectasis colonized by different bacterial species sensitive for tobramycin. Objective: The primary outcome of the study is a 50% reduction in exacerbation rate in patients using maintenance TIS (OD). Secondary outcome parameters are lung function (FEV1, FVC), QoL (QOL-B), LTRI-VAS, Leicester cough score, bacterial load in sputum and tobramycin resistant pathogens. Study design: A randomised, double blind placebo controlled, multicenter study. Study population: Patients aged ≥ 18-year-old with confirmed bronchiectasis by (HR)CT and at least two exacerbations during previous 12 months.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: TIS 300mg once daily<br>Tobramycin inhalation solution (TIS) 300mg once daily for at least 9 months and up to 12 months | Drug: tobramycin inhalation solution<br> <br> |
| Placebo Comparator: Placebo once daily<br>Saline 0.9% inhalation solution 300mg once daily for at least 9 months and up to 12 months | Drug: Saline 0.9% inhalation solution<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of exacerbations |  | 13 months |