RETHINC: REdefining THerapy In Early COPD for the Pulmonary Trials Cooperative
Condition: COPD (Chronic Obstructive Pulmonary Disease)
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Intervention: Indacaterol/Glycopyrrolate; Placebo
Intervention description: 27.5/15.6 mcg active indacaterol/glycopyrrolate; 27.5/15.6 mcg placebo
Intervention MeSH terms: Glycopyrrolate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 780.0
Sex: All
Minimum age: 40 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: COPD; Chronic Obstructive Pulmonary Disease; Pulmonary Function Tests; Current Smoker; Former Smoker; Chronic Obstructive Airway Disease; Respiratory Symptoms

Summary:

      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.
    

Eligibility criteria:

        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             x-ray to be no longer active), or clinically significant bronchiectasis.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).