Characteristics of the double blind randomised clinical trials included in the analysis
| Study | Duration of trial/no randomised/pre-randomisation run-in | Inclusion criteria/exclusion criteria/participant characteristics | Permitted co-therapies/discontinued co-therapies(% on co-therapy at baseline) | Control group intervention(s) |
|---|---|---|---|---|
| py, pack years; MI, myocardial infarction; CHF, congestive heart failure; NA, not available; URI, upper respiratory infection; SABA, short acting bronchodilator; LABA, long acting bronchodilator; MDI, metered dose inhaler. | ||||
| Beeh20 | 12 weeks N = 1639 1 week washout period | Inclusion: COPD, FEV1 ⩽70% predicted, ratio ⩽70%, age >40 years, smoking history >10 py | Permitted: SABA (76%), inhaled corticosteroid (57%), prednisone (16%), theophylline (52%) Discontinued: ipratropium (69%), LABA (50%) | Placebo |
| Exclusion: asthma, allergic rhinitis, atopy, oxygen use, arrhythmia, recent MI or CHF hospitalisation | ||||
| Characteristics: Mean age 62 years; 75% male; FEV1: 1.3 (0.5) l; FVC 2.4 (0.7) l;ratio NA | ||||
| Brusasco17 | 6 months N = 1207 2 week washout period | Inclusion: COPD, FEV1 ⩽65% predicted, ratio ⩽70%, age >40 years, smoking history >10 py Exclusion: asthma, allergic rhinitis, atopy, total eosinophil count ⩾600/mm3, oxygen use, URI <6 weeks, other significant disease Characteristics: Mean age 64 years; 76% male; FEV1 1.1 (0.4) l; FVC 2.6 (0.7) l;ratio 43 (10)% | Permitted: NA (Donohue30 lists SABA (66%), inhaled corticosteroid (66%), prednisone (6%), theophylline (21%)) | (1) Salmeterol 50 μg bid by MDI(2) Placebo |
| Discontinued: NA (Donohue30 lists ipratropium (53%), LABA (NA)) | ||||
| Briggs16 | 12 weeks N = 653 2 week washout period | Inclusion: COPD, FEV1 ⩽60% predicted, ratio ⩽70%, age >40 years, smoking history >10 py | Permitted: SABA (58%), inhaled corticosteroid (50%), prednisone (2%) Discontinued: ipratropium (55%), LABA (47%), theophylline (12%) | Salmeterol 50 μg bid by MDI |
| Exclusion: asthma, allergic rhinitis, atopy, total eosinophil count ⩾600/mm3, renal insufficiency, prostatic hypertrophy, glaucoma, other significant disease, COPD exacerbation <4 weeks, prednisone ⩾10 mg/day, β blockers, oxygen use, recent pulmonary rehabilitation | ||||
| Characteristics: Mean age 64 years; 66% male; FEV1 1.0 (0.4) l; FVC 2.4 (0.7) l;ratio 43 (10)% | ||||
| Casaburi19 | 12 months N = 921 2 week washout period | Inclusion: COPD, FEV1 ⩽65% predicted, ratio ⩽70%, age ⩾40 years, smoking history >10 py Exclusion criteria: asthma, allergic rhinitis, atopy, total eosinophil count ⩾600/mm3,oxygen use, prednisone ⩾10 mg in prior month, MI <1 year, CHF <3 years, arrhythmia Characteristics: Mean age 65 years; 65% male; FEV1 1.0 (0.4) l; FVC 2.3 (0.8) l;ratio 46 (12)% | Permitted: SABA (99%), inhaled corticosteroid (42%), prednisone (7%), theophylline (23%) | Placebo |
| Discontinued: ipratropium (57%), LABA (NA) | ||||
| Casaburi30 | 25 weeks N = 108 1 week training run-in | Inclusion: COPD, FEV1 ⩽60% predicted, ratio ⩽70%, age ⩾40 years, smoking history >10 py, able to perform pulmonary rehabilitation | Permitted: SABA, inhaled and prednisone, theophylline (% NA) Discontinued: ipratropium, LABA (% NA) | Placebo |
| Exclusion: asthma, allergic rhinitis, atopy, total eosinophil count ⩾600/mm3, BMI<18 or >30 kg/m2, other significant disease, recent URI, MI, CHF, arrhythmia | ||||
| Characteristics: Mean age 67 years; 56% male; FEV1 0.9 (0.4) l; FVC% 34 (12);ratio 43 (11)% | ||||
| Dusser21 | 48 weeks N = 1050 3 week run-in | Inclusion: COPD, pre-BD FEV1 30-65% predicted, FEV1/SVC ⩽70%, age >40 years,smoking history >10 py, ⩾1 exacerbation in prior year | Permitted: SABA (94%), inhaled corticosteroid (63%), prednisone (2%) Discontinued: ipratropium (38%), LABA (32%), theophylline (7%) | Placebo |
| Exclusion: asthma, allergic rhinitis, atopy, renal insufficiency, oxygen use, COPD exacerbation<6 weeks, prednisone ⩾10 mg/day, other significant medical illness | ||||
| Characteristics: Mean age: 65 years; 88% male; FEV1 1.4 (0.4) l; FVC 2.6 (0.8) l;ratio 55 (12)% | ||||
| Niewoehner18 | 6 months N = 1829 No run-in period | Inclusion: COPD, FEV1 ⩽60% predicted, ratio ⩽70%, age >40 years, smoking history >10 py Exclusion: asthma, renal insufficiency, prostatic hypertrophy, glaucoma, MI <6 months, arrhythmia, CHF hospitalisation <1 year, on cancer treatment, COPD exacerbation<4 weeks, prednisone ⩾20 mg/day | Permitted: SABA (94%), LABA (38%), inhaled corticosteroid (58%),prednisone (10%), theophylline (14%), oxygen (29%) Discontinued: ipratropium (80%) | Placebo |
| Characteristics: Mean age 68 years; 99% male; FEV1 1.0 (0.4) l; ratio 48 (11)% | ||||
| Verkindre31 | 12 weeks N = 100 2 weeks run-in | Inclusion: COPD, FEV1 ⩽50% predicted, FEV1/SVC ⩽70% predicted, RV ⩽125%predicted, age >40 years, smoking history >10 py, ⩾1 exacerbation in previous year | Permitted: SABA, inhaled and prednisone, theophylline (% NA) Discontinued: ipratropium, LABA (% NA) | Placebo |
| Exclusion: asthma, allergic rhinitis, atopy, total eosinophil count ⩾600/mm3, MI<1 year, arrhythmia, CHF <3 years, oxygen use, COPD exacerbation <6 weeks,prednisone ⩾10 mg/day | ||||
| Characteristics: Mean age 59 years; 94% male; FEV1 1.1 (0.3) l; FVC 2.4 (0.7) l;ratio 40 (7)% | ||||
| Vincken15 | 12 months N = 535 2 week washout period | Inclusion: COPD, FEV1 ⩽65% predicted, ratio ⩽70%, age ⩾40 years, smoking history >10 py Exclusion: asthma, allergic rhinitis, atopy, total eosinophil count ⩾600/mm3, oxygen use, recent URI, other significant disease (van Noord32 lists MI <1 year, CHF <3 years,arrhythmia, prostatic hypertrophy, glaucoma, anticholinergic drug allergy) | Permitted: SABA (76%), inhaled corticosteroid (80%), prednisone (9%), theophylline (16%) Discontinued: ipratropium (60%), LABA (NA) | Ipratropium 40 μg qid by MDI |
| Characteristics: Mean age 64 years; 85% male; FEV1 1.2 (0.4) l; FVC 2.7 (0.8);ratio 46 (10)% | ||||