Inhaled colistimethate sodium in patients with bronchiectasis and Pseudomonas aeruginosa infection: results of PROMIS-I and PROMIS-II, two randomised, double-blind, placebo-controlled phase 3 trials assessing safety and efficacy over 12 months

作者：Charles Haworth, Michal Shteinberg, Kevin Winthrop, Alan R. Barker, Francesco Blasi, Katerina Dimakou, Lucy Morgan, Anne E. O’Donnell, Felix C. Ringshausen, Oriol Sibila, Rachel Thomson, Kevin J. Carroll, Federica Pontenani, Paola Castellani, James D. Chalmers · 发表于：The Lancet Respiratory Medicine · 年份：2024 · DOI：10.1016/s2213-2600(24)00225-x · 被引用次数：28 · 研究领域：Cystic Fibrosis Research Advances、Bacterial biofilms and quorum sensing、Pediatric health and respiratory diseases

BACKGROUND: Chronic lung infection with Pseudomonas aeruginosa is associated with increased exacerbations and mortality in people with bronchiectasis. The PROMIS-I and PROMIS-II trials investigated the efficacy and safety of 12-months of inhaled colistimethate sodium delivered via the I-neb. METHODS: Two randomised, double-blind, placebo-controlled trials of twice per day colistimethate sodium versus placebo were conducted in patients with bronchiectasis with P aeruginosa and a history of at least two exacerbations requiring oral antibiotics or one requiring intravenous antibiotics in the previous year in hospitals in Argentina, Australia, Belgium, Canada, France, Germany, Greece, Israel, Italy, Netherlands, New Zealand, Poland, Portugal, Spain, Switzerland, the UK, and the USA. Randomisation was conducted through an interactive web response system and stratified by site and long term use of macrolides. Masking was achieved by providing colistimethate sodium and placebo in identical vials. After random assignment, study visits were scheduled for 1, 3, 6, 9, and 12 months (the end of the treatment period); and telephone calls were scheduled for 7 days after random assignment and 2 weeks after the end of treatment. The primary endpoint was the mean annual exacerbation rate. These trials are registered with EudraCT: number 2015-002743-33 (for PROMIS-I) and 2016-004558-13 (for PROMIS-II), and are now completed. FINDINGS: 377 patients were randomly assigned in PROMIS-I (177 to col...