Cystic FibrosisPhase 2RATNONCT02295566
RATNO, Reducing Antibiotic Tolerance Using Nitric Oxide in CF - a Phase 2 Pilot Study
A Phase 2 study testing Nitric Oxide in people with Cystic Fibrosis, run by University Hospital Southampton NHS Foundation Trust at 1 site in United Kingdom.
Trial 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". Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- Nitric Oxide
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- May 2011to Jul 2013
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Adolescents and young adults with cystic fibrosis aged 12 or above
- Colonised with Pseudomonas aeruginosa (confirmed on sputum sample)
Who cannot join
- 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)
Show all 13Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University Southampton NHS Foundation Trust
Southampton, Hampshire, SO16 6YD
About this study
Official title: RATNO (Reducing Antibiotic Tolerance Using NO) Reducing Antibiotic Tolerance Using Low Dose Nitric Oxide in Cystic Fibrosis - a Phase 2 Pilot Study
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.
Read more
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.
Read the detailed description
Not required
- Conditions
- Cystic Fibrosis
- Being tested
- Nitric Oxide, Control
- Keywords
- Nitric Oxide, Pseudomonas Aeruginosa, Biofilm
- Medical subject headings
- Cystic Fibrosis, Pseudomonas Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitric OxideDrug
Not required
ControlDrug
Also called Air, Oxygen
Not required
| Study group | Role | What they receive |
|---|---|---|
| Nitric Oxide Group | Active comparator | Inhaled Nitric Oxide delivered via nasal canulae at 10ppm for 8 hours a night for 7 nights. Receives: Drug: Nitric Oxide |
| Control Group | Placebo comparator | Air/oxygen mix (according to clinical need) delivered via nasal canulae for 8 hours a night for 7 nights. Receives: Drug: Control |
What is being measured
The primary outcome is the main question the study is designed to answer.
Biovolume of Pseudomonas Aeruginosa (PA) biofilms in sputum
Assessment of PA biofilms using FISH and image analysis, colony forming units and quantitative polymerase chain reaction.
Measured: 2 years
Secondary outcomes (6)
Bacterial density
To estimate the effect of adjunctive low dose inhaled nitric oxide given with standard antibiotic therapy on the whole community of bacteria within the CF lung by determination of CFU counts on non-selective agar.
Measured: 2 years
Forced Expiratory Volume in 1 second (FEV1)
To assess the effect of NO on lung function measured by FEV1
Measured: 2 years
Nitric Oxide levels in sputum
To estimate the NO levels in sputum in each group.
Measured: 2 years
Bacterial species identification
To determine the characteristics in the wider microbial community within the CF lung using molecular methods during an exacerbation and to compare these characteristics between the two groups.
Measured: 5 years
Exhaled Nitric Oxide
To assess the effect of low dose inhaled nitric oxide on exhaled nitric oxide levels
Measured: 2 years
Health related quality of life score (HRQOL)
To assess the effect of low dose inhaled nitric oxide on HRQOL using the Cystic Fibrosis Questionnaire - United Kingdom (CFQ-UK).
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2014 (estimated)
- Study startMay 2011
- Primary completionDec 2012
- Study completionJul 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Southampton NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- University of Southampton
- Responsible party
- Sponsor
- Investigators
- Saul Faust, Principal investigator, University Hopsital Southampton NHS Foundation TrustGary Connett, FRCPCH MD, Study director, University Hospital Southampton NHS Foundation TrustJeremy Webb, PhD, Study director, Universityh of Southampton
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02295566
- Sponsor's protocol ID
- RHM CHI0548
- Other IDs
- 2010-023529-39, 11/H0502/7
- Acronym
- RATNO
- Status last verified
- Nov 2014
- First submitted
- 20 Aug 2014
- Last updated
- 30 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RATNO (Reducing Antibiotic Tolerance Using NO) Reducing Antibiotic Tolerance Using Low Dose Nitric Oxide in Cystic Fibrosis - a Phase 2 Pilot Study
- ClinicalTrials.gov ID
- NCT02295566
- Acronym / sponsor ID
- RATNO / RHM CHI0548
- Conditions
- Cystic Fibrosis
- Keywords
- Nitric Oxide, Pseudomonas Aeruginosa, Biofilm
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University Hospital Southampton NHS Foundation TrustUniversity, hospital or other
- Collaborators
- University of Southampton
- Study start
- May 2011
- Primary completion
- Dec 2012 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 20 Nov 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Not required
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nitric Oxide Group | Active comparator | Drug: Nitric OxideInhaled Nitric Oxide delivered via nasal canulae at 10ppm for 8 hours a night for 7 nights. |
| Control Group | Placebo comparator | Drug: ControlAir/oxygen mix (according to clinical need) delivered via nasal canulae for 8 hours a night for 7 nights. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Adolescents and young adults with cystic fibrosis aged 12 or above
- Colonised with Pseudomonas aeruginosa (confirmed on sputum sample)
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nitric OxideNot required | Drug | Nitric Oxide Group |
| ControlAlso: Air, OxygenNot required | Drug | Control Group |
Primary outcome
Biovolume of Pseudomonas Aeruginosa (PA) biofilms in sputum
Time frame: 2 years
Assessment of PA biofilms using FISH and image analysis, colony forming units and quantitative polymerase chain reaction.
6 secondary outcomes
Bacterial density
Time frame: 2 years
Forced Expiratory Volume in 1 second (FEV1)
Time frame: 2 years
Nitric Oxide levels in sputum
Time frame: 2 years
Bacterial species identification
Time frame: 5 years
Exhaled Nitric Oxide
Time frame: 2 years
Health related quality of life score (HRQOL)
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2024.
- Published resultsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Saul Faust principal investigator
University Hopsital Southampton NHS Foundation Trust
Gary Connett, FRCPCH MD study director
University Hospital Southampton NHS Foundation Trust
Jeremy Webb, PhD study director
Universityh of Southampton
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nitric Oxide in people with Cystic Fibrosis, run by University Hospital Southampton NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Biovolume of Pseudomonas Aeruginosa (PA) biofilms in sputum (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 May 2024.