RCT Abstract - The efficacy and safety of colistimethate sodium delivered via the I-neb in bronchiectasis: the PROMIS-I randomized controlled trial

Non-cystic fibrosis bronchiectasis is a debilitating chronic condition with no approved treatments in which chronic <i>Pseudomonas aeruginosa</i> infection is associated with substantially increased morbidity and mortality. The PROMIS-I trial investigated the efficacy and safety of 12 months of therapy with inhaled colistimethate sodium delivered via the I-neb (CMS I-neb). A randomised, double-blind, placebo-controlled trial of twice daily CMS I-neb (delivered dose of 0.3ml of 1 MIU in 1ml 0.45% saline) vs placebo (0.3ml 0.45% saline) was conducted in 12 countries in patients with <i>P. aeruginosa</i> in sputum at screening and at least 2 exacerbations or 1 requiring IV antibiotics in the previous year. The primary endpoint was mean exacerbation rate over 12 months. 377 patients were randomised, 177 to CMS I-neb and 200 to placebo. The annual rate of exacerbations was lower in patients receiving CMS I-neb vs placebo (0.58 per patient per year vs 0.95, rate ratio (RR) 0.61 95% CI 0.46-0.82, p=0.00101). There was a prolonged time to first exacerbation in the CMS I-neb group (HR 0.59, 95% CI 0.43-0.81, p=0.00074). Severe exacerbations were also reduced (RR 0.41 95% CI 0.23-0.74, p=0.003). The percentage of patients with adverse events was similar between groups. Bronchospasm and antibiotic resistance were infrequently observed (2.8% and 1% respectively). CMS I-neb significantly reduced the annual rate of exacerbations and severe exacerbations in patients with bronchiectasis and <i>P. aeruginosa</i>. Treatment was safe and well tolerated.