Two replicate randomised, double-blind, placebo-controlled trials
Treatment
Inhaled colistimethate sodium via the I-neb adaptive aerosol delivery system
Control
Placebo
Population
377 patients in PROMIS-I and 287 in PROMIS-II with bronchiectasis and Pseudomonas aeruginosa infection
Follow-up
12 months
Primary endpoint
Annual rate of pulmonary exacerbations
Result
PROMIS-I: 0.58 exacerbations per year with colistimethate versus 0.95 with placebo (rate ratio 0.61, 95% CI 0.46 to 0.82, p=0.0010). PROMIS-II did not replicate this; it was terminated prematurely and disrupted by the COVID-19 pandemic.
Secondary endpoints
Time to first exacerbation, quality of life, Pseudomonas density
The data from PROMIS-I suggest a clinically important benefit of colistimethate sodium delivered via the I-neb adaptive aerosol delivery system in patients with bronchiectasis and P aeruginosa infection. These results were not replicated in PROMIS-II, which was affected by the COVID-19 pandemic and prematurely terminated.
The trial authors, in the published abstract
How it has aged
A split verdict, honestly reported. PROMIS-II's failure has a plausible explanation in premature termination and pandemic disruption, but a replicate that does not replicate is exactly the situation in which to be cautious. Inhaled antibiotics in bronchiectasis remain a reasonable option rather than a settled one.
Publications
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
Haworth CS, Shteinberg M, Winthrop K, et al. 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. Lancet Respir Med 2024 Oct;12(10):787-798.
39% reduction in exacerbation rate in PROMIS-I
No significant effect in PROMIS-II, which was terminated early during the pandemic