| Methods |
Study Design: Parallel RCT
Randomisation: computer generated
Concealment of Allocation: opaque consecutive numbered envelopes
Double Blinding: Yes
Withdrawals / dropouts: described
Adverse events: described
Statistical analysis: described
Jadad Score: 5 |
| Participants |
Study site: Multi‐centred
No eligible: 77
No randomised: 34 (15/19)
No completed: 34
Sex: Males: 15 (44%); Females:19 (56%)
Age: mean 43.9 yrs; range: 19‐65yrs
Diagnostic criteria for asthma: Clinically diagnosed asthma defined by ATS criteria
Inclusion criteria: stable asthma (according to predefined criteria), controlled on ICS (BDP or BUD) of 800‐1600mcg/day; symptoms of episodic cough , wheezing and dyspnoea for > 1 year prior to Visit 1; reversible airway obstruction with >=15% reversibility with bronchodilator;positive PC20 documented up to 6 months prior to study;20% PEF diurnal variation; FEV1 > 60% predicted; adults 18‐65 yrs.
Exclusion criteria: excluded if remained stable when ICS was withdrawn during the sensitivity period.
Baseline severity of asthma: mean FEV1: 2.9L; mean FEV1 % predicted: 86.4%; Mean BDP dose at study entry: 1224mcg/day; smokers: 14(41%); atopy:15 (44%). |
| Interventions |
Run in phase: 2 weeks with BDP dose equivalent to maintenance ICS to assess stability.
Run in phase 2: 'sensitivity period': BDP reduced by 200mcg/week until asthma became unstable according to predefined criteria. Minimal acceptable dose (MAD) BDP determined as the dose one step above the dose precipitating unstable asthma. Those remaining stable after ICS withdrawal excluded from study.
Run in phase 3: given 3 times MAD for 2 weeks then if stable randomised to:
1: Salmeterol 50mcg bd , OR
2: Placebo
AND ICS dose reduction repeated and MAD determined.
Run out phase: 2 weeks follow‐up on appropriate ICS at conclusion of study.
Delivery device: DPI
Duration of treatment: Max 14 weeks
Other: salbutamol prn |
| Outcomes |
ICS dose, morning & evening PEF, FEV1, day a& nighttime symptom scores, rescue medication, adverse events |
| Notes |
Comparison 2: Reduced dose ICS |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Adequate sequence generation? |
Low risk |
Computer generated randomisation schedule |
| Allocation concealment? |
Low risk |
Opaque consecutive numbered envelopes |
| Blinding?
All outcomes |
Low risk |
Identical inhaler devices used |
