CompletedPhase 2

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

United Kingdom12 participantsStarted 2011-05

Plain-language 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.

Who can participate

Age range

12 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * Adolescents and young adults with cystic fibrosis aged 12 or above * Colonised with Pseudomonas aeruginosa (confirmed on sputum sample) Exclusion Criteria: * Colonisation with Burkholderia cepacia * Known hypersensitivity to the antibiotics used in the study * Other known contraindications to the antibiotics to be used in the study including known aminoglycoside related hearing/renal damage * Patients requiring non-invasive ventilation (NIV) * Patients who have a pneumothorax * Patients who are admitted for specific treatment of nontuberculous mycobacteria (NTM) * Patients who cannot tolerate nasal cannula e.g. those who cannot breathe through their nose * Patients who have nasal polyposis that is causing significant blockage of the nasal passages * Adolescents who are not Gillick competent (and therefore not able to give their own assent in addition to parental consent) * Patients not likely to survive the time period of the study washout period (4 months from enrolment) * Treatment with an investigational drug or device within the last 3 months prior to enrolment * Patients who are pregnant (a pregnancy test will be carried out for females of 11 years and above as is standard practice for clinical trials) * Immediate families of investigators or site personnel directly affiliated with the study. Immediate family is defined as child or sibling, whether biological or legally adopted.

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Biovolume of Pseudomonas Aeruginosa (PA) biofilms in sputum

Timeframe: 2 years

Trial details

NCT IDNCT02295566

SponsorUniversity Hospital Southampton NHS Foundation Trust

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2012-12

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