Holgate 2004a.
| Methods | Randomised, double‐blind, parallel‐group multi‐centre placebo‐controlled trial. Randomisation by computer‐generated randomisation after run‐in. Allocation by independent personnel. Scratch cards given to investigators to be broken in case of emergency | |
| Participants | N = 246. Treatment group: 126; control group: 120 (two withdrawals due to keratitis and dysphonia—communication from Acumed). Mean age (placebo): 40.5 (12 to 71); treatment group: 41.1 (12 to 75). Female/Male percentage: placebo: 57.5/42.5; treatment: 64.3/35.7. Severe asthmatic participants optimally controlled, requiring high‐dose fluticasone. FP dose: between 1000 and 2000 mcg/d Inclusion criteria stated as: male/females 12 to 75 years of age, severe asthma according to ATS guidelines, allergic response (> one positive skin prick test to one or more aeroallergens, mean total daily symptom score ≥ four over seven days before randomisation, ≥ 12% reversibility, FEV1 within 30 minutes of salbutamol in 12 months before or at randomisation, stable medication four weeks before randomisation, IgE between 30 and 700 IU/mL Exclusion criteria stated as: females for whom current or future pregnancy could not be excluded, evidence/history of drug or alcohol abuse, history of non‐compliance with medical regimens, those considered potentially unreliable, known sensitivity to study drugs (omalizumab, corticosteroids, salbutamol and terbutaline), those using theophylline, those suffering from live/kidney disease, haematological abnormality, anaphylaxis, near‐fatal asthma exacerbation in last three years, elevated serum IgE for reasons other than atopy (parasitic infections, etc). Baseline data: mean duration of disease: placebo: 22.3 years; treatment: 22.6 years. Never smoked/ex‐smokers: placebo: 91/29; treatment: 99/27. Mean serum total IgE levels (IU/mL): placebo: 265.7 (±190.2); treatment: 266.8 (±218.0). Mean fluticasone dose (mcg/d): placebo: 1362.5 (±359.2); treatment: 1375 (±361.6). Participants taking LABA: placebo: 52 (43%); treatment: 62 (49%). Mean FEV1 (percentage predicted): placebo: 66 (±20.2); treatment: 62.9 (±17.5). Mean FEV1 reversibility: placebo: 20.6; treatment: 18.6. PEFR: placebo: 385.2; treatment: 371.9 |
|
| Interventions | Subcutaneous omalizumab (0.016 mg/kg/IgE (IU/mL) at two‐ or four‐weekly intervals depending on body weight versus placebo. Four‐phase study. SIx‐ to 10‐week run‐in phase, 16‐week steroid stable phase, 16‐week steroid reduction phase, 12‐week follow‐up | |
| Outcomes | Percentage reduction from baseline in inhaled FP, number of participants achieving > 50% reduction in inhaled fluticasone (subgroup according to LABA consumption), exacerbations, PEFR, QoL | |
| Notes | Jadad score: 5 Trial 011 | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Randomisation by computer‐generated randomisation after run‐in |
| Allocation concealment (selection bias) | Low risk | Allocation by independent personnel |
| Blinding (performance bias and detection bias) All outcomes | Low risk | Double‐blind |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 18 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 |