The prevention of airway narrowing following dry powder mannitol inhalation in susceptible bronchiectatic patients
In bronchiectatic patients susceptible to airway narrowing after inhaling dry powder mannitol is a single dose of sodium cromoglycate or eformoterol more effective than placebo in preventing airway narrowing
Sydney South West Area Health Service
25 participants
Aug 20, 2007
Interventional
Conditions
Summary
Dry powder mannitol has the potential to be prescribed as a treatment for bronchiectasis because of its demonstrated ability to enhance mucociliary clearance. However, some bronchiectatic patients demonstrate airway narrowing after inhaling mannitol. If pre-medicating these patients with either sodium cromoglycate or eformoterol can be shown to protect them from developing significant airway narrowing after inhaling mannitol, this patient population may be able to access a potential new treatment for their disease.
Eligibility
Inclusion Criteria1
- Subjects must: 1) Have given written informed consent to participate in this study, 2) Have symptomatic (i.e. daily production of sputum) non-cystic fibrosis (CF) bronchiectasis, confirmed by high resolution computed tomography (HRCT), 3) Be a non smoker, 5) Be able to perform reproducible spirometry, 4) Have an FEV1 1.2 Litres, 5) Be in a stable clinical condition at the time of, and for a period of 14 days prior to, recruitment into the study, 6) Have a positive response to inhaled mannitol, as measured by a fall in FEV1 of 15% after < 315mg of mannitol on Visit 1
Exclusion Criteria1
- Subjects must not: 1) Have bronchiectasis as a consequence of cystic fibrosis or focal endobronchial lesion, 2) Be considered “terminally ill” or listed for lung transplantation, 3) Have had a significant episode of haemoptysis (>60 mL) in the previous six months, 4) Have had an exacerbation for which they have been prescribed intravenous antibiotics in the 4 weeks prior to study entry, 5) Have a smoking history of >20 pack years or have smoked more than one cigarette a week within the previous three months, 6) Have had a myocardial infarction in the three months prior to enrolment, 7) Have had a cerebral vascular accident in the three months prior to enrolment, 8) Have had major ocular surgery in the three months prior to enrolment, 9) Have had major abdominal, chest or brain surgery in the three months prior to enrolment, 10) Have a known cerebral, aortic or abdominal aneurysm, 11) Have active tuberculosis, 12) Have active malignancy including melanoma (other skin carcinomas and remissions exempted), 13) Be breast feeding or pregnant, or plan to become pregnant while in the study, 14) Be using an unreliable form of contraception (female subjects at risk of pregnancy only), 15) Be participating in another investigative drug study, parallel to, or within 4 weeks of study entry, 16) Have a known intolerance to mannitol or ß-agonists, 17) Have uncontrolled hypertension – systolic BP > 190 and/or diastolic BP > 100, 18) Have resting oximetry of less than 90%, 19) Have a condition or be in a situation which in the Investigator’s opinion may put the subject at significant risk, may confound results or may interfere significantly with the patient’s participation in the study.
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Interventions
At a screening visit subjects will be asked to perform a mannitol challenge test in order to determine if their airways narrow significantly in response to the inhalation of up to 635mg of dry powder mannitol. During the challenge test, subjects will be asked to inhale mannitol from a series of capsules using a simple, dry powder inhaler: the Osmohaler. The challenge begins with a 5mg dose of mannitol, and this dose is gradually increased over a series of steps. At each step lung function (spirometry) will be measured before moving on to the next dose. Mannitol will cause the airways to narrow if the subject has hyperresponsive airways. The challenge test will stop either when the breathing tests show that the subject’s airways function is 15% less than when the test started or after 635mg of mannitol has been inhaled. After the challenge test, if the subject’s airways have narrowed, they will be given bronchodilator (200ug salbutamol, i.e.Ventolin, inhaled from a metered dose inhaler via a large volume spacer, the Volumatic) and recovery will be monitored by spirometry. If recovery to within 5% of baseline has not occurred within 15 minutes further doses of Ventolin will be given every 15 minutes until recovery to within 5% of baseline. Upon satisfying all inclusion/exclusion criteria for the study subjects will be asked to return for a further 3 treatment visits, with a washout period of 3 or more days separating each visit. During these visits subjects will be pre-medicated with either placebo (used as a control), 20mg sodium cromoglycate or 12ug eformoterol fumarate dihydrate 15 minutes prior to performing a mannitol challenge test. The challenge test will proceed as described above. Please note that the sodium cromoglycate, eformoterol fumarate dihydrate, placebo and mannitol will all be inhaled in dry powder form using an Aerolizer dry powder inhaler.
Locations(1)
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ACTRN12607000379415