Effects of long term ToBrAmycin InhalaTion SoluTion (TIS) once daiLy on Exacerbation rate in patients with non-cystic fibrosis bronchiectasis. A doubleblind, randomized, placebo controlled trial. The BATTLE study.

Rationale:

Patients with bronchiectasis often have exacerbations of their disease. These exacerbations influence the quality of life. In patients with cystic fibrosis (CF) inhaled antibiotics lower the bacterial load in bronchial secretions and have a positive effect on the number of exacerbations, lung function and quality of life (QoL). In patients with non-CF bronchiectasis colonized with Pseudomonas aeruginosa, studies with tobramycin inhalation solution (TIS) are limited. In present study the value of TIS will be investigated in patients with non-CF bronchiectasis colonized by Gram-negative bacteria and/or Staphylococcus aureus in sputum.

Methods:

In this multicenter, double-blind, randomized, placebo controlled study, TIS 300 mg OD will be compared to placebo OD during 12 months. Patients will be randomized 1: 1. Patients are included who are aged ≥18-year-old with confirmed bronchiectasis by (HR) CT and at least two exacerbations during the previous 12 months. For the study schedule see figure 1.

Results:

The hypothesis of the study is a 50% reduction in exacerbation rate in patients with prolonged treatment of tobramycin (OD) in a patient group with 2 or more exacerbations per year. This reduction represents clinical relevance and is based on the assumption that maintenance treatment with TIS will be comparable to that of systemic azithromycin treatment. This assumption is derived from data of the BAT trial. In order to determine a statistical difference of p < 0.05, with a power of 0.80, and a drop-out percentage of 30%, 26 patients will be allocated on each treatment arm. Secondary outcome parameters are lung function (FEV1, FVC), QoL (QOL-B, LTRI-VAS, Leicester cough score), bacterial load in sputum and tobramycin resistant pathogens.

Conclusions:

The primary outcome of the study is a 50% reduction in exacerbation rate in patients with non-CF bronchiectasis using TIS (OD) compared to placebo. A total number of 52 patients will be included.

This study design was earlier presented at the ATS, San Francisco, May 2016.

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