E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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?
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the trial is the last visit (follow-up at T20-25) of the last subject randomised in the trial. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |