This is a multi-center, randomized, 36-month, parallel- group, non-inferiority, phase III study to compare the effectiveness of roflumilast 500 mcg daily versus azithromycin (250 mg QD or 500 mg QD three times per week) to prevent hospitalization or death in patients at high risk for COPD exacerbations.

Both drugs are FDA approved, however the current evidence base does not offer a definitive answer as to which agent should be used in patients susceptible to exacerbations.  It is a low touch remote trial that will guide the treating and referring physician as to the randomization assignment and management of prescription. No on-site visits to Oakland required by patient. It is a pragmatic, real world study where clinicians retain the flexibility to alternate regimens, titrate up or down, cross over, or combine the treatment at any time if clinically indicated. Medications will not be provided to patients; clinicians will prescribe the medications and ask patients to fill prescriptions as per usual.

Primary End-Point: