RETHINC: REdefining THerapy In Early COPD for the Pulmonary Trials Cooperative
RETHINC: REdefining THerapy In Early COPD for the Pulmonary Trials Cooperative
The study hypothesis is that symptomatic current and former smokers with spirometric values
 within the normal range (post-bronchodilator FEV1/FVC≥0.70 and post-BD FVC ≥ 70% predicted
 will still derive symptomatic benefit from long-acting bronchodilator therapy even though
 they are excluded from current GOLD guideline recommendations.
RETHINC is a 12-week multicenter, randomized, double-blind, placebo-controlled,
 parallel-group study to assess the efficacy and safety of indacaterol/glycopyrrolate
 27.5/15.6 mcg inhaled twice daily in symptomatic current and former smokers with respiratory
 symptoms despite preserved spirometry as defined by CAT ≥ 10 and post-bronchodilator FEV1/FVC
 ratio ≥0.70, respectively.
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 x-ray to be no longer active), or clinically significant bronchiectasis.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).