RATNO, Reducing Antibiotic Tolerance Using Nitric Oxide in CF - a Phase 2 Pilot Study

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.

Conditions

• Cystic Fibrosis

Interventions

DRUG

Nitric Oxide

Not required

DRUG

Control

Not required

Sponsors & Collaborators

• University of Southampton

  collaborator OTHER

• University Hospital Southampton NHS Foundation Trust

  lead OTHER

Principal Investigators

• Saul Faust · University Hopsital Southampton NHS Foundation Trust

• Gary Connett, FRCPCH MD · University Hospital Southampton NHS Foundation Trust

• Jeremy Webb, PhD · Universityh of Southampton

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

12 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2011-05-31

Primary Completion

2012-12-31

Completion

2013-07-31

Countries

• United Kingdom

Study Locations