RCT Abstract - Inhaled colistimethate sodium in patients with bronchiectasis and Pseudomonas aeruginosa infection: Results of two randomized double-blind placebo-controlled phase 3 trials assessing safety and efficacy over 12 months

The PROMIS-I and -II trials investigated the efficacy and safety of 12-months of inhaled colistimethate sodium (CMS) delivered via the I-neb. <bold>Methods:</bold> Two randomised, double-blind, placebo-controlled trials of twice-daily CMS vs placebo were conducted in bronchiectasis patients with <italic>P. aeruginosa</italic> and a history of at least 2 exacerbations requiring oral antibiotics or 1 requiring intravenous antibiotics in the previous year. The primary endpoint was the mean annualised exacerbation rate. Findings: 377 patients were randomized in PROMIS-I (CMS:176, Placebo:197). The annualised exacerbation rate was 0.58 in CMS vs 0.95 in placebo treated patients (rate ratio (RR) 0.61 95%CI 0.46-0.82, p=0.001). 287 patients were randomized in PROMIS-II before it was prematurely terminated due to the impact of the COVID-19 pandemic (CMS:152, Placebo:135). There was no difference in the annualised exacerbation rate between CMS and placebo patients (0.89 vs 0.89, RR 1.0 95%CI 0.75-1.35, p=0.98). No major safety issues were identified. The overall frequency of adverse events was 142 (80.7%) in the CMS groups vs 159 (80.7%) in the placebo group in PROMIS-I and 123 (80.9%) vs 104 (77.0%) in PROMIS-II. Interpretation: The data from PROMIS-I suggest a clinically important benefit of CMS delivered via the I-neb in patients with bronchiectasis and <italic>P. aeruginosa</italic> infection. These results were not replicated in PROMIS-II which was impacted by the COVID-19 pandemic and prematurely terminated.