Reducing antibiotic tolerance using low dose nitric oxide in cystic fibrosis – a phase 2 pilot study - RATNO (Reducing Antibiotic Tolerance using Nitric Oxide in CF) v 1.0

• Register: EUCTR
• Last refreshed on: 16 October 2012
• Main ID: EUCTR2010-023529-39-GB
• Date of registration: 31/12/2010
• Prospective Registration: Yes
• Primary sponsor: Southampton University Hopsitals NHS Trust
• Public title: Reducing antibiotic tolerance using low dose nitric oxide in cystic fibrosis – a phase 2 pilot study - RATNO (Reducing Antibiotic Tolerance using Nitric Oxide in CF) v 1.0
• Scientific title: Reducing antibiotic tolerance using low dose nitric oxide in cystic fibrosis – a phase 2 pilot study - RATNO (Reducing Antibiotic Tolerance using Nitric Oxide in CF) v 1.0
• Date of first enrolment: 18/02/2011
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-023529-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: yes Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
• Adolescents and young adults with cystic fibrosis aged 12 or above
• Colonised with Pseudomonas aeruginosa (50% or more of all cultures in the last 12 months positive for Pseudomonas aeruginosa)

Criteria for randomisation:
• Requiring antibiotic therapy for a pulmonary exacerbation:

A pulmonary exacerbation will be defined according to the criteria published by the 1994 cystic fibrosis foundation microbiology and infectious disease consensus and used in recent large clinical trials.

The presence of 3 of the following 11 criteria:
? Increased cough
? Increased sputum production, change in appearance of expectorated sputum production, or both
? Fever (greater than or equal to 38°C for at least 4 hrs in a 24 hrs period) on more than one occasion in the previous week
? Weight loss greater than or equal to 1kg or 5% of bodyweight associated with anorexia and decreased dietary intake
? School or work absenteeism (due to illness) in the previous week
? Increased respiratory rate, increased work of breathing, or both
? New findings on chest examination (e.g. rales, wheezing, crackles)
? Decreased exercise tolerance
? Decrease in FEV1 of greater than or equal to 10% from previous baseline study within the past 3 months
? Decrease in haemoglobin saturation (as measured by oximetry) from baseline value within past 3 months of greater than or equal to 10%
? New finding on chest radiograph

Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 canula 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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Cystic Fibrosis

Intervention(s)

Trade Name: INOmax 400ppm mol/mol inhalation gas
Product Name: Nitric Oxide
Product Code: NO
Pharmaceutical Form: Inhalation gas

Primary Outcome(s)

Secondary Objective: Laboratory

1. To compare the effect of low dose inhaled nitric oxide and placebo on the amount of PA bacteria in sputum.

2. To estimate the effect of low dose inhaled nitric oxide given with standard antibiotic therapy on the whole community of bacteria within the CF lung.

3. To estimate the NO levels in sputum in each group.

4. To look at the types and variety of bacteria in the wider community of bacteria found in the CF lung during an exacerbation and to compare this between the two groups.

Clinical

1. To assess the effect of inhaled NO on lung function measured by FEV1.

2. To assess the effect of low dose inhaled nitric oxide on exhaled nitric oxide levels.

3. To assess the effect of low dose inhaled nitric oxide on Health Related Quality Of Life using the CFQ-UK?

4. To determine the appropriate clinical endpoints for a future larger trial of nitric oxide in participants with CF undergoing IV antibiotic therapy for an exacerbation?

Main Objective: The primary objective of this pilot study is to see whether giving low dose inhaled nitric oxide in addition to standard intravenous antibiotic therapy (during a pulmonary exacerbation in patients with cystic fibrosis) will increase the effectiveness of the antibiotic therapy due to the disruption and killing of microcolonies of Pseudomonas aeruginosa (PA) bacteria.

Primary end point(s): Between group differences in proportion of bacteria in biofilms (as determined by live/dead staining, direct visualisation of the biofilm and image analysis) between T0 and T20-25.

Secondary ID(s)

n/a

RHM CHI 0548