A Double-Blind Randomized Placebo-Controlled Phase 3 Trial of Tobramycin Inhalation Solution in Adults With
Wei-Jie Guan1, Jin-Fu Xu2, Hong Luo3
1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China; Department of Thoracic Surgery, Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Background:
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.
Research Question:
Can TIS effectively reduce sputum P aeruginosa density and improve the bronchiectasis-specific quality of life in patients with bronchiectasis with P aeruginosa infection?
Study Design And Methods:
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 (300 mg/5 mL twice daily) or normal saline (5 mL twice daily) via vibrating-mesh nebulizer. Treatment consisted of two cycles, each consisting of 28 days on-treatment and 28 days off-treatment. The coprimary end points included changes from baseline in P aeruginosa density and Quality-of-Life Bronchiectasis Respiratory Symptoms score on day 29.
Results:
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 P aeruginosa 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 P aeruginosa in the tobramycin group than in the placebo group on day 29 (29.3% vs 10.6%). The incidence of adverse events and serious adverse events were comparable between the two groups.
Interpretation:
TIS is an effective treatment option and has an acceptable safety profile in patients with bronchiectasis with P aeruginosa infection.
Trial Registration:
ClinicalTrials.gov; No. NCT03715322; URL: www.
Clinicaltrials:
gov.
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