aminar airflow in severe asthma for exacerbation reductio
- Conditions
- AsthmaRespiratory
- Registration Number
- ISRCTN46346208
- Lead Sponsor
- Queen Alexandra Hospital (UK)
- Brief Summary
2016 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/26743812 2019 results in: https://www.ncbi.nlm.nih.gov/pubmed/31232684 (added 25/06/2019)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 240
Current inclusion criteria as of 24/07/2015:
1. Adults (aged 16-75 years inclusive)
2. A clinical diagnosis of asthma for =6 months supported by evidence of any one of the following:
2.1. Airflow variability with a mean diurnal peak expiratory flow (PEF) variability >15% during the baseline 2-week period or a variability in FEV1 of >20% across clinic visits within the preceding 12 months, with concomitant evidence of airflow obstruction (FEV1/FVC ratio <70%);
2.2. Airway reversibility with an improvement in FEV1 by =12% or 200 ml after inhalation of 400 µg of salbutamol via a metered dose inhaler and spacer at first study visit or within the preceding 12 months;
2.3. Airway hyper-responsiveness demonstrated by Methacholine challenge testing with a provocative concentration of Methacholine required to cause a 20% reduction in FEV1 (PC20) of =8mg/ml or equivalent test (See Appendix 3).
3. Severe asthma:
3.1. Requirement for high-dose inhaled corticosteroids (ICS) (=1000µg/day beclomethasone (BDP) or equivalent – see Appendix 4) plus a second controller (long-acting ß2-agonist or anti-muscarinic, theophylline, or leukotriene antagonist), and/or systemic corticosteroids.
3.2. If on maintenance corticosteroids, the maintenance dose must have been stable for 3-months– this excludes any interim need for short-term steroid bursts to treat exacerbations.
4. Poorly controlled asthma demonstrated by BOTH:
4.1. =2 severe asthma exacerbations, requiring systemic corticosteroids =30mg prednisolone or equivalent daily (or =50% increase in dose if maintenance 30mg prednisolone or above), for 3 or more days, during the previous 12 months, despite the use of high-dose inhaled corticosteroids (ICS) and additional controller medication;
4.2. ACQ (7-point) score >1 at Screening Visit 1 and Randomisation Visit 2.
5. Atopic status:
5.1. Sensitisation to =1 perennial indoor aeroallergen[2] (including House Dust Mite, domestic pet or fungi) to which they are likely to be exposed during the study, demonstrated by a positive skin prick test (wheal diameter =3mm more than negative control) or specific IgE =0.35 IU/L).
6. Exacerbation free and taking stable maintenance asthma medications (not including short-acting bronchodilator or other reliever therapies) for at least 2-weeks prior to Screening Visit 1
7. Exacerbation free and taking stable maintenance asthma medications (not including short-acting bronchodilator or other reliever therapies) in the period between Screening Visit 1 and Randomisation Visit 2.(the Screening Period). Participants suffering a severe exacerbation during the Screening Period can be rescreened 2 weeks after returning to their maintenance asthma medications (See 11.3.2)
8. Able to use the TLA device during sleep on at least five nights per week (excluding holidays)
9. Able to understand and give written informed consent prior to participation in the trial and able to comply with the trial requirements
Previous inclusion criteria:
1. Adults (aged 18-75 years inclusive)
2. A clinical diagnosis of asthma for =6 months prior to trial entry supported by evidence of either:
2.1. Airflow variabili
1. Current smokers or ex-smokers abstinent for <6 months
2. Ex-smokers with =15 pack year smoking history
3. Partner who is a current smoker and smokes within the bedroom where the TLA device is installed
4. TLA device cannot be safely installed within the bedroom, intending to move out of study area within the trial period or unable to use the TLA device for at least 8 hours on at least 5 nights per week
5. Documented poor treatment adherence
6. Occupational asthma with continued exposure to known sensitising agents in the workplace
7. Previous bronchial thermoplasty within 12 months
8. Maintenance treatment with Omalizumab (anti-IgE) within 3 months
9. Using long-term oxygen, Continuous Positive Airway Pressure (CPAP) or Non-Invasive Ventilation (NIV) routinely overnight as this will impair the effect of the TLA device
10. Uncontrolled symptomatic gastro-oesophageal reflux that may act as a persistent asthma trigger
11. Presence of clinically significant lung disease other than asthma, including smoking-related chronic obstructive pulmonary disease (COPD), bronchiectasis associated with recurrent bacterial infection, allergic bronchopulmonary aspergillosis (mycosis), pulmonary fibrosis, sleep apnoea, pulmonary hypertension, or lung cancer
12. Patients with clinically significant co-morbidity (including cardiovascular, endocrine, metabolic, gastro-intestinal, hepatic, neurological, renal, haematological and malignant conditions) that remains uncontrolled with standard treatment
13. Patients currently taking part in other interventional clinical trials
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The primary efficacy end point in this study, the rate of clinically significant exacerbations over the 12-month period, will be modelled as a Poisson random variable. A Poisson regression model with an adjustment for over-dispersion will be used to compare the rate of asthma exacerbations between the two groups with log of time used as an offset variable. Further analysis will adjust for the baseline characteristics including the ACQ score, age, BMI and sex. Intention to treat (ITT) analysis will be performed on the primary outcome on all participants who will be randomised. The study results will be reported in accordance with the CONSORT (Consolidated Standards of Reporting Trials) 2010 statements. Stata (or equivalent stats package) will be used for all the analyses. All the tests will be done at a 5% two-sided significance level.
- Secondary Outcome Measures
Name Time Method