Exacerbation and Symptom Control After Pseudomonas Eradication Treatment in Adult Bronchiectasis: a multicentre randomized controlled trial (ESCAPE)

Research summary

This trial will determine future guideline recommendations for patients with bronchiectasis. P. aeruginosa is difficult to treat and patients are at high risk of hospitalization, lung function decline and death (4,5) Preventing long term P. aeruginosa infection is therefore highly desirable. The NHS spends more than £30m annually on managing bronchiectasis (8). A US study comparing healthcare costs before and after acquisition of P. aeruginosa reported an 87% increase from $36,213 to $67,764 annually per patient (10,11). Determining the efficacy of P. aeruginosa eradication treatment was the top research priority identified in a prioritisation exercise involving a survey of European bronchiectasis experts and 711 patients with bronchiectasis, published in 2017 (12). A systematic review and meta-analysis (CRD42021287027) of studies of P. aeruginosa eradication therapy in bronchiectasis was carried out. Eligible publications were identified by searching MEDLINE and EMBASE. Studies in cystic fibrosis were excluded. Study endpoints were P. aeruginosa eradication from sputum at 12 months and frequency of exacerbations. Random-effects meta-analysis was used to pool individual studies. 212 studies were identified. No randomized controlled trials were identified. After applying the inclusion and exclusion criteria, six single-centre observational studies were selected for the meta-analysis corresponding to a total of 287 patients. The meta-analysis found a 12-month P. aeruginosa eradication rate of 42% 95%CI 36-47%; p<0.00001 with no significant heterogeneity. Five studies provided data allowing a subgroup analysis to test whether the specific antibiotic regimen (“combined systemic and inhaled antibiotics” or “systemic antibiotics”) modifies the effect. The eradication rate for combined therapy was 48% (95%CI 41-55%) while systemic antibiotics alone provided an efficacy of 27% (13-45%). The test of subgroup interaction was statistically significant (p=0.01). In two studies(14,16), there was a significant reduction in exacerbation rate post-eradication but the limited data precluded firm conclusions regarding exacerbation benefit. It was concluded that there is insufficient data to establish the efficacy of eradication treatment. There are no randomized trials in bronchiectasis and existing observational studies are small and at high risk of bias. The existing evidence supports the ERS guideline recommendations to include inhaled antibiotics as part of the regimen, since systemic antibiotics alone are associated with low eradication rates (9) This has informed the study design to compare systemic plus inhaled antibiotics with symptomatic treatment.

Principal Investigator

Dr William Flowers

Contact us

Email: catherine.borg@ouh.nhs.uk

Phone: 01865227242

IRAS number

1011311