RATNO (Reducing Antibiotic Tolerance using Nitric Oxide in CF) v 1.0

• Research type

  Research Study

• Full title

  Reducing antibiotic tolerance using low dose nitric oxide in cystic fibrosis – a phase 2 pilot study

• IRAS ID

  63126

• Contact name

  Saul Faust

• Sponsor organisation

  Southampton University Hospital Research and Development

• Eudract number

  2010-023529-39

• ISRCTN Number

  n/a

• Clinicaltrials.gov Identifier

  n/a

• Research summary

  The lungs of most patients with cystic fibrosis become infected with bacteria called Pseudomonas aeruginosa during childhood. This infection is now known to consist of free-living bacteria and bacteria in colonies on body surfaces known as “biofilms”. The bacteria in biofilms are more resistant and tolerant to antibiotics. Current CF treatment of exacerbations aims to eradicate or control pseudomonal infection using aggressive antibiotic regimes. Despite this treatment many patients develop chronic infection which is never cleared and causes damage to the lungs. Patients colonised with Pseudomonas are more unwell and die at a younger age. Our laboratory has established that low dose nitric oxide (NO) can disrupt pseudomonal biofilms in the laboratory. This study will discover whether non-toxic levels of NO will disrupt bacteria from biofilms and increase the effectiveness of antibiotic therapy. This is a participant-blind, randomised controlled pilot study of treatment with nitric oxide gas during an acute infective exacerbation. Patients with CF (>12 years) will be asked to take part. They will be randomised to receive 7 days of either inhaled nitric oxide gas or placebo (air) given via nasal cannula overnight alongside standard IV antibiotic therapy during an exacerbation. Sputum samples will be obtained before, during and after treatment for analysis. The primary endpoint will be the microbiological effect on bacterial biofilms before and after NO therapy. Secondary endpoints will take the form of detailed microbiological and clinical analysis, including: between group differences in pseudomonal colony forming units (CFU??s), biofilm NO levels and detailed characterisation of biofilms before and after treatment as well as lung function and quality of life. The aim of this randomised pilot study is as proof of concept and to guide the design of a large multi-centre trial to definitively evaluate the effectiveness of NO as adjunctive therapy in CF.

• REC name

  South Central - Hampshire A Research Ethics Committee

• REC reference

  11/H0502/7

• Date of REC Opinion

  18 Feb 2011

• REC opinion

  Further Information Favourable Opinion