Oborne 2009.
| Methods | This randomised, double‐blind, placebo‐controlled, parallel‐group study investigated whether a 4‐fold increase in the dose of inhaled corticosteroids, started when asthma control deteriorates, can prevent the need for oral corticosteroids | |
| Participants |
Population 403 participants were randomised and 94 participants experienced an exacerbation, for a total of 121 exacerbations contributed to the analysis Participants 16 years of age or older. Mean age was 56 years. 32% of participants were male. 10% were smokers, 21% ex‐smokers and 69% never‐smokers Baseline asthma severity Mean ICS dose: 520 mcg Mean FEV1: 2.2 L or 82% predicted Mean PEFR: 380 L/min Inclusion criteria: age > 16 years, stable asthma, treated with ICS (200 to 1000 mcg budesonide or equivalent), taken a course of oral corticosteroid or doubled dose of ICS in the previous 12 months but not in the preceding 4 weeks Exclusion criteria: > 20 pack‐year smoking history, other clinically significant medical conditions, pregnant or lactating |
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| Interventions |
Run‐in period: 2‐week period whereby participants continued their usual dose of inhaled corticosteroid and recorded morning peak flow and daytime symptom scores to ensure asthma stability Study period Control arm: maintenance inhaled corticosteroid (200 to 1000 mcg/d) + identical placebo inhaler for exacerbations Study arm: maintenance inhaled corticosteroid (200 to 1000 mcg/d) + identical inhaler with corticosteroid to quadruple dose of ICS for exacerbations Participants were to use study inhaler for 14 days in addition to usual treatment when peak flow or symptoms deteriorated Other medications allowed Not specified |
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| Outcomes |
Primary outcome Number of partcipants who had exacerbations of asthma treated with oral corticosteroids (ITT analysis) Secondary outcomes Number of participants who started the study inhaler and went on to require treatment with oral corticosteroids (per‐protocol or modified ITT analysis) |
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| Notes | Funding source: Asthma UK | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | "An allocation sequence of random permuted blocks of 10 was generated using a random number table by an independent pharmacist and implemented by one of the study investigators once participants were enrolled into the trial" |
| Allocation concealment (selection bias) | Low risk | Independent pharmacist randomly allocated individuals; "The authors thank…Sarah Pacey for providing the randomization schedule and concealed allocation of masked inhalers" |
| Blinding (performance bias and detection bias) All outcomes | Low risk | "double‐blind, placebo‐controlled trial" ‐ "Drug groups were labelled as A, B, C, and D to mask statisticians to treatment group during the first complete run‐through of data analyses" ‐ "Active and placebo inhalers were…identical apart from the presence or absence of inhaled corticosteroid, to achieve allocation concealment and blinding of investigators and participants" |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Thirty‐eight (19.3%) and 39 participants (18.9%) in the active and placebo groups withdrew from the study but contributed data for the intention‐to‐treat analysis up to the point at which they left the study. All participants received their allocated intervention, although 3 were lost to follow‐up with no outcome data (all in the placebo group), leaving 197 and 203 participants in the groups receiving active and placebo inhalers, respectively, for the intention‐to‐treat analysis |
| Selective reporting (reporting bias) | Low risk | Outcomes reported match those stated in the prospectively registered protocol and are relevant to the review |