RETHINC: REdefining THerapy In Early COPD for the Pulmonary Trials Cooperative

Inclusion Criteria: 1. Subject must be able to understand and provide informed consent 2. Age 40-80 3. ≥10 pack-year smoking history 4. Post-bronchodilator FEV1/FVC ratio ≥0.70 5. Baseline CAT≥10 Exclusion Criteria: 1. Inability or unwillingness of a participant to give written informed consent or comply with study protocol. 2. Subject is pregnant, breast-feeding, or plans to become pregnant. 3. Active pulmonary infection or prior pulmonary infection where antibiotic and/or steroid treatment was completed ≤4 weeks prior to enrollment. 4. Post-BD FVC \< 70% predicted 5. A primary diagnosis of asthma established by each study investigator based on ATS/ERS criteria as previously implemented in the MACRO clinical trial. 6. Known concomitant lung disease, pulmonary tuberculosis (unless confirmed by chest x-ray to be no longer active), or clinically significant bronchiectasis. 7. History (or family history) of long QT syndrome. 8. History of paroxysmal (intermittent) atrial fibrillation will be considered an exclusion. Patients with persistent atrial fibrillation as defined by continuous atrial fibrillation for at least 6 months and controlled with a rate control strategy (i.e., selective beta blocker, calcium channel blocker, pacemaker placement, digoxin or ablation therapy) for at least 6 months may be considered for inclusion. In such patients, heart rate at enrollment must be \< 100/min. 9. Patients with BMI \< 15 or more than 40 kg/m2. 10. Patients with diabetes Type I or uncontrolled diabetes Type II. 11. Patients who, in the judgment of the investigator, have a clinically relevant laboratory abnormality or a clinically significant condition such as (but not limited to) significant renal disease, psychiatric disease, gastrointestinal disease, unstable ischemic heart disease, arrhythmia (excluding chronic stable atrial fibrillation), uncontrolled hypertension or any other condition which in the opinion of investigator might compromise patient safety or compliance, interfere with evaluation, or preclude completion of the study. 12. Patients with any history of lung cancer. 13. Patients with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia or bladder-neck obstruction or severe renal impairment or urinary retention. Benign Prostatic Hyperplasia (BPH) patients who are stable on treatment can be considered. 14. Any other past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study. 15. Patients with a history of hypersensitivity to any of the study drugs or to drugs from similar chemical classification, including untoward reactions to sympathomimetic amines or inhaled medication or any component thereof. 16. Patients unable to successfully use a dry powder inhaler device or perform spirometry measurements. 17. Use of other investigational drugs at the time of enrollment or within 30 days or 5 half-lives of enrollment, whichever is longer. 18. Patients receiving any protocol-specified prohibited medications.. 19. Patients receiving any protocol-specified prohibited COPD related medications (will be required to undergo a required washout period prior to enrollment).