INNOVATE.
Methods | Randomised, double‐blind, parallel‐group, multi‐centre, placebo‐controlled trial. Blinding: matched placebo. Methods of allocation not reported. Randomisation stratified by concomitant asthma treatment and country of origin | |
Participants | N = 482. Mean age: omalizumab: 43.4; placebo: 43.3. FEV1: omalizumab: 61; placebo: 61.6; rescue medication usage: omalizumab: 6.6; placebo: 5.5. Overall AQLQ: 3.9 (both groups); serum total IgE: omalizumab: 197.6; placebo: 189.6; ICS dose (BDP equivalent, mcg/d): omalizumab: 2359; placebo: 2301. All participants receiving high‐dose ICS + LABA. 22% receiving maintenance oral steroids Inclusion criteria: +ve skin prick test to ≥ one aeroallergen; serum IgE: 30 to 700 IU/mL; severe persistent asthma requiring > 1000 BDP or equivalent and LABA treatment; FEV1 40% to 80%; FEV1 reversibility ≥ 12% post SABA; ≥ two exacerbations requiring OCS in previous 12 months or one severe exacerbation resulting in hospitalisation Exclusion criteria: smokers/smoking history of ≥ 10 pack‐years; treatment for exacerbation four weeks before randomisation; use of methotrexate/gold salts/troleandomycin/cyclosporin within three months of first visit; prior omalizumab treatment |
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Interventions | Subcutaneous omalizumab (0.016 mg/kg per IU/mL) (plus usual care) versus placebo (plus usual care). Study duration: 28 weeks; run‐in phase: seven‐day screening period; eight‐week run‐in phase. Follow‐up: 16‐week (data not presented). During initial four weeks of run‐in phase, medicines adjusted to achieve best control. No further adjustments permitted in last four weeks of run‐in | |
Outcomes | Exacerbatrions (requiring OCS); hospitalisation; emergency room treatment; lung function; AQLQ; adverse events | |
Notes | Jadad score: 4. Imbalance between groups at baseline for primary outcome in the trial. Greater instance of exacerbations requiring oral steroids in omalizumab group compared with placebo group. Adjusted data were extracted and entered | |
Risk of bias | ||
Bias | Authors' judgement | Support for judgement |
Random sequence generation (selection bias) | Unclear risk | Randomisation stratified by concomitant asthma treatment and country of origin |
Allocation concealment (selection bias) | Unclear risk | Methods of allocation not reported |
Blinding (performance bias and detection bias) All outcomes | Low risk | Double‐blind |
Incomplete outcome data (attrition bias) All outcomes | Low risk | 52 participants did not complete the trial, and reasons for withdrawal are included in the trial report |
Selective reporting (reporting bias) | Unclear risk | No apparent indication of selective reporting bias |