A Double-Blind Randomized Placebo-Controlled Phase 3 Trial of Tobramycin Inhalation Solution in Adults With Bronchiectasis With Pseudomonas aeruginosa Infection

Abstract

Few large-scale studies have demonstrated the efficacy of tobramycin nebulization in bronchiectasis. We evaluated the efficacy and safety of nebulized tobramycin inhalation solution (TIS) in adults with bronchiectasis with Pseudomonas aeruginosa infection. Can TIS effectively reduce sputum Paeruginosa density and improve the bronchiectasis-specific quality of life in patients with bronchiectasis with Paeruginosa infection? This was a phase 3, 16-week, multicenter, randomized, double-blind, placebo-controlled trial. Eligible adults with bronchiectasis were recruited from October 2018 to July 2021. On the basis of usual care, patients nebulized TIS (300mg/5mL twice daily) or normal saline (5mL twice daily) via vibrating-mesh nebulizer. Treatment consisted of two cycles, each consisting of 28days on-treatment and 28days off-treatment. The coprimary end points included changes from baseline in Paeruginosa density and Quality-of-Life Bronchiectasis Respiratory Symptoms score on day29. The modified intention-to-treat population consisted of 167 patients in the tobramycin group and 172 patients in the placebo group. Compared with placebo, TIS resulted in a significantly greater reduction in Paeruginosa density (adjusted mean difference, 1.74 log10 colony-forming units/g; 95%CI, 1.12-2.35; P< .001) and greater improvement in Quality-of-Life Bronchiectasis Respiratory Symptoms score (adjusted mean difference, 7.91; 95%CI, 5.72-10.11; P< .001) on day 29. Similar findings were observed on day 85. TIS resulted in a significant reduction in 24-h sputum volume and sputum purulence score on days 29, 57, and 85. More patients became culture negative for Paeruginosa in the tobramycin group than in the placebo group on day 29 (29.3%vs10.6%). The incidence of adverse events and serious adverse events were comparable between the two groups. TIS is an effective treatment option and has an acceptable safety profile in patients with bronchiectasis with Paeruginosa infection. ClinicalTrials.gov; No. NCT03715322; URL: www. gov.