The proposed study is a randomized, placebo-controlled trial and will be conducted through the existing NIH COPD Clinical Research Network. 1028 patients with at least moderately severe COPD (post bronchodilator forced expiratory volume/forced vital capacity (FEV1/FVC) < 70%, post bronchodilator FEV1 < 80% predicted, with or without chronic symptoms will be randomized. Participants will be males and females 40-80 years of age with cigarette consumption of 10 pack years or more. Based on our experience from prior similar trials we will enrich the population for patients likely to have acute exacerbations.
Patients with resting bradycardia, who are already taking beta-blockers or have an absolute indication for their use, will be excluded. Patients will undergo a screening clinic visit at which time eligibility will be determined. Patients will return to the clinic to be randomized and receive blinded study drug within 14 days of screening. They will return to the clinic for dose titration visits and then follow up visits at weeks 16, 32 and 48 to assess safety and efficacy. After 48 weeks of treatment, investigational drug will be tapered off over 4 weeks. Phone calls to patients will be made at regular intervals throughout the trial to query exacerbation events. Intention to treat analysis will be used to determine the effect of metoprolol on the time to first exacerbation.