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

Cystic Fibrosis Clinical Trial

— RATNO  

Official title:

RATNO (Reducing Antibiotic Tolerance Using NO) Reducing Antibiotic Tolerance Using Low Dose Nitric Oxide in Cystic Fibrosis - a Phase 2 Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02295566
• Other study ID #: RHM CHI0548
• Secondary ID: 2010-023529-3911
• Status: Completed
• Phase: Phase 2
• Start date: May 2011
• Est. completion date: July 2013

Study information

• Verified date: November 2014
• Source: University Hospital Southampton NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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". 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.

Description:

Not required

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: July 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• Nitric Oxide
Not required
• Control
Not required

Locations

Country	Name	City	State
United Kingdom	University Southampton NHS Foundation Trust	Southampton	Hampshire

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital Southampton NHS Foundation Trust	University of Southampton

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	2 years
Secondary	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.	2 years
Secondary	Forced Expiratory Volume in 1 second (FEV1)	To assess the effect of NO on lung function measured by FEV1	2 years
Secondary	Nitric Oxide levels in sputum	To estimate the NO levels in sputum in each group.	2 years
Secondary	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.	5 years
Secondary	Exhaled Nitric Oxide	To assess the effect of low dose inhaled nitric oxide on exhaled nitric oxide levels	2 years
Secondary	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).	2 years

External Links

•   Published results