RATNO, Reducing Antibiotic Tolerance Using Nitric Oxide in CF - a Phase 2 Pilot Study
Status:
Completed
Trial end date:
2013-07-01
Target enrollment:
Participant gender:
Summary
The lungs of most patients with cystic fibrosis (CF) become chronically infected with
bacteria called Pseudomonas aeruginosa during childhood. This infection is now known to
consist of free-living bacteria (known as "planktonic 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.
Chronic infection 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 pilot study will discover
whether non-toxic levels of NO administered to participants during an episode of acute
infection (exacerbation) will disrupt bacteria from biofilms and increase the effectiveness
of antibiotic therapy. This protocol describes a participant-blind randomised controlled
pilot study of treatment with nitric oxide gas during an acute infective exacerbation (also
known simply as an "acute exacerbation"). Patients with CF aged 12 or above will be asked to
take part.
They will be randomised to receive 7 days either of inhaled nitric oxide gas or placebo
alongside standard therapy during an exacerbation. Sputum samples will be obtained before,
during and after the treatment period for microbiological analysis. The primary endpoint will
be the microbiological effect on bacterial biofilms before and after NO adjunctive therapy.
Secondary microbiological endpoints will include the between group differences in pseudomonal
colony forming units (CFU"s), biofilm NO levels and detailed characterisation of biofilms
before and after treatment.
Secondary clinical endpoints will include lung function and well-established indicators
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 or
NO donors as adjunctive therapy in CF.
Phase:
Phase 2
Details
Lead Sponsor:
University Hospital Southampton NHS Foundation Trust