Fitzgerald 2004.
| Methods | This 6‐month, multi‐centre, randomised, double‐blind, placebo‐controlled, parallel‐group study compared a continued maintenance dose of inhaled corticosteroid vs a dose doubled at the time of an asthma exacerbation Conducted at 4 teaching units in Canada |
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| Participants |
Population 290 participants were randomised; 98 participants experienced an exacerbation and contributed to the analysis Participants were 13 years or older. Mean age was 32 years. 28% were male. 14% were ex‐smokers of fewer than 10 pack‐years, and 86% were non‐smokers Baseline asthma severity Mean dose of budesonide: 635 mcg Mean FEV1: 2.8 L Mean PEFR: 423 L/min At least 1 previous asthma exacerbation with mean duration from recent exacerbation to visit 1 of 131 days Stable dose of ICS (< 1200 mcg/d of beclomethasone or equivalent twice daily) for 1 month before visit 1 Inclusion criteria Age ≥ 13; documentation of the diagnosis of asthma within the previous year based on FEV1 reversibility post bronchodilator, methacholine provoking a fall in FEV1 and/or diurnal PEF variability Exclusion criteria Severe or near fatal asthma; current smokers and ex‐smokers > 10 pack‐years; baseline use of LABA; pregnant or lactating women; women of child‐bearing potential not on effective birth control; exacerbation due to chronic sinusitis; hospitalisation in previous 3 months; respiratory tract infection ≤ 1 month before visit 1 |
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| Interventions |
Run‐in period Three‐ to six‐week period whereby participants using other forms of inhalers were switched to budesonide turbuhaler at an equivalent dose and placed on a twice‐daily dose regimen Study period Control arm: maintenance inhaler of budesonide (100, 200 or 400 mcg BID) + placebo inhaler BID for exacerbations Study arm: maintenance inhaler of budesonide + inhaler with budesonide to double dose of ICS (200, 400 or 800 mcg BID) for exacerbations Other medications allowed Terbutaline sulphate inhaler as rescue medication; theophylline; anticholinergics; nasal corticosteroids |
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| Outcomes |
Primary outcome The proportion of participants with treatment failure as judged by the need for treatment with oral methylprednisolone or an unscheduled visit to a physician or medical emergency department due to asthma or unstable asthma after 14 days of treatment Secondary outcomes None |
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| Notes | Funding source: AstraZeneca Canada Inc. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | "Patients were randomised to treatment groups at visit 2 according to a blocked computer generated randomisation list for each centre" |
| Allocation concealment (selection bias) | Low risk | Central randomisation ‐ assumed that this meant randomisation was separate from those dealing with participant details |
| Blinding (performance bias and detection bias) All outcomes | Low risk | "Double‐blind trial" ‐ "The maintenance dose (MD) group received a maintenance inhaler of budesonide dispensing 100, 200, or 400 mg/dose (depending on their maintenance therapy) plus an additional inhaler containing placebo for twice daily use. The double dose (DD) group received the same maintenance inhaler as the first group, but the additional inhaler dispensed 100, 200, or 400 mg/dose of budesonide as well" |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | "Statistical analysis used the "all patients treated" (APT) approach. Since patients were "treated" only if they had an exacerbation, all patients who had at least one asthma exacerbation after randomisation and were treated with at least one dose of additional study drug are included" ‐ Of the 148 randomised to the control group, 115 completed the study (22% dropout), and 117/142 in the intervention group completed the study (17.6% dropout). This was considered relatively low and balanced |
| Selective reporting (reporting bias) | Low risk | The primary outcome and outcomes of interest to this review were well reported. Some secondary outcomes not relevant to our review were presented only graphically. Peak expiratory flow rate data not reported for unforeseen technical reasons. These data were not required as a pre‐defined primary or secondary outcome |