Dasgupta 2016.

Study characteristics
Methods	Phase 3, randomised, double‐blind, placebo‐controlled study Study location: Firestone Institute of Respiratory Health, St Joseph's Hospital, Hamilton, Ontario, Canada, L8N 4A6
Participants	19 participants aged 40 to 80 years with a diagnosis of COPD with eosinophilic bronchitis were randomised into 2 study arms. 1 participant (from placebo group) left the study just after randomisation because of severe exacerbation requiring hospitalisation, therefore the study was conducted in 18 participants. Mepolizumab 750 mg: 8 participants, mean age 65.1 years (SD 6.3); females 4 (50%). Placebo: 10 participants, mean age 66.9 years (SD 5.9); females 1 (10%). Inclusion criteria: Diagnosis: an established clinical history of COPD in accordance with the definition by the ATS/ERS as follows: COPD is a preventable and treatable disease state characterised by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and is associated with an abnormal inflammatory response of the lungs to noxious particles or gases, primarily caused by cigarette smoking. Although COPD affects the lungs, it also produces significant systemic consequences. Sputum eosinophils > 3% at randomisation and on at least 1 occasion in the past 2 years. If these historic data are not available, documented improvement in FEV₁ of at least 12% with a course of prednisone in the past 2 years will be used as a surrogate for the presence of airway eosinophilia. FEV₁/FVC < 70% and FEV₁ < 60% of predicted normal values calculated using NHANES III reference equations at screening visit. At least 1 major exacerbation requiring prednisone in the preceding 12 months. If patients are currently well controlled by optimising their sputum cell counts (eosinophils < 2%), they should have documented history of exacerbations when their eosinophilia was uncontrolled. A signed and dated written informed consent prior to study participation. Smoking history: current or former cigarette smokers with a history of cigarette smoking of greater than 10 pack‐years (number of pack years = (number of cigarettes per day/20) x number of years smoked (e.g. 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years)). Former smokers are defined as those who have stopped smoking for at least 6 months prior to screening visit. Male or female adults. A female is eligible to enter and participate in the study if she is either of non‐childbearing potential, or is of childbearing age and has a negative pregnancy test at screening and agrees to acceptable contraceptive methods used consistently and correctly. Exclusion criteria: Current asthma (12% reversibility to a bronchodilator). Sputum eosinophils < 3% on fluticasone (or equivalent) of 250 µg twice a day. Inability to use salmeterol or tiotropium. Significant comorbidity that prevents participation in the study. Known bronchiectasis or immune deficiency disorders that would predispose the individual to recurrent infections. Pregnancy or intent to become pregnant and lactating females. Drug or alcohol abuse: a known or suspected history of alcohol or drug abuse within 2 years prior to screening visit.
Interventions	Mepolizumab 750 mg versus placebo. Mepolizumab (an anti‐IL‐5, given once a month intravenously at a dose of 750 mg). The placebo consisted of 100 mL normal saline solution (0.9%, 154 mmol/L sodium chloride).
Outcomes	Primary outcome measures: Percentage decrease of sputum eosinophils from baseline. Time Frame: 6 months Secondary outcome measures: Proportion of participants with a major exacerbation. Time Frame: 6 months
Notes	Principal Investigator: Parameswaran Nair, MD, PhD, FRCP. Associate Professor of Medicine, Division of Respiratory, McMaster University Sponsor: McMaster University
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information in the trial report to permit a judgement.
Allocation concealment (selection bias)	Unclear risk	Insufficient information in the trial report to permit a judgement.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	This is clearly stated in clinicaltrials.gov/show/NCT01463644.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	This is clearly stated in clinicaltrials.gov/show/NCT01463644.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Insufficient information in the trial report to permit a judgement.
Selective reporting (reporting bias)	Unclear risk	Insufficient information in the trial report to permit a judgement.
Other bias	High risk	The inclusion criteria for this study required < 12% FEV₁ reversibility to a bronchodilator. It appears that some participants were entered despite not meeting this criterion, therefore it is likely that some people in this study had current asthma.