GLOW1 2011.

Methods	Design: double‐blind, placebo‐controlled study Duration: 26 weeks (+ 7 day pre‐screening period and 14 day run‐in) Location: 97 centres in 11 countries
Participants	Population: 822 participants were randomised to glycopyrronium (552) and placebo (270) Baseline characteristics Age (mean years): gly 63.8, pbo 64.0 % Male: gly 82.5, pbo 80.5 % FEV1 predicted: gly 54.8, pbo 54.3 Pack‐years (mean): gly 44.9, pbo 44.6 Inclusion criteria: Patients with COPD with a smoking history of >10 pack‐years, post‐bronchodilator forced expiratory volume in 1 second (FEV1) < 80% and . 30% predicted normal and FEV1/forced vital capacity < 0.70 Exclusion criteria: lower respiratory tract infection within 6 weeks, concomitant pulmonary disease, history of asthma, lung cancer or long QT syndrome or QTc > 450 ms (males) or > 470 (females), symptomatic prostatic hyperplasia, bladder‐neck obstruction, moderate/ severe renal impairment, urinary retention, narrow angle glaucoma and history of alpha‐1 antitrypsin deficiency. Patients were also excluded if they were participating in a supervised pulmonary rehabilitation programme, had contraindications for tiotropium or ipratropium or had experienced adverse reactions to inhaled anticholinergics.
Interventions	1. Glycopyrronium bromide 50 qd (LAMA) 2. Placebo (PBO) Inhaler device: low‐resistance single‐dose dry‐powder inhaler (Breezhaler) Allowed co‐medications: inhaled/intranasal corticosteroids and H1 antagonists were permitted in patients stabilized on them prior to study entry. Patients were required to cease taking long‐acting bronchodilator therapy before beginning the run‐in period
Outcomes	The primary outcome measure was trough FEV1 at Week 12. Secondary outcome measures included breathlessness on the transition dyspnoea index (TDI) and health‐related quality of life (HRQoL) according to the St. George’s Respiratory Questionnaire (SGRQ) at Week 26, time to first moderate or severe COPD exacerbation and mean daily rescue medication use over 26 weeks.
Notes	Funding: Novartis Identifier(s): NCT01005901
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	randomized in a 2:1 ratio [sequence generation not described, but industry funded so presumed electronic]
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) [clinicaltrials.gov]
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) [clinicaltrials.gov]
Incomplete outcome data (attrition bias) All outcomes	Low risk	Dropout was relatively even and around 20% in both groups. Efficacy was based on centralized spirometry and assessed in the full analysis set (FAS), which included all randomized patients who received at least one dose of study drug; patients were analysed according to the treatment to which they were randomized. The last observation of pre‐dose trough FEV1 was carried forward (LOCF) for missing values.
Selective reporting (reporting bias)	Low risk	Full results were available from the published report and on clinicaltrials.gov in accordance with the protocol