Compare the Effects of Nebulizer Versus Inhaler Based Therapy for COPD Using Long-acting Bronchodilators

This is a prospective, randomized, parallel group, double dummy, phase four, 13-week clinical trial with 1:1 allocation comparing long-acting anti-muscarinic agent (LAMA; Umeclidinium 62.5 μg once daily) and long acting beta-agonist (LABA; Vilanterol 25 μg once daily) delivered by DPI (Group A), vs a nebulized LAMA/LABA combination (revefenacin 175 μg once daily and formoterol 20 μg twice daily) (Group B) among symptomatic subjects with stable COPD.

The study begins with a screening visit and run-in period. Patients who are eligible and willing to participate will sign informed consent. They will be trained on the use of the DPI and nebulizer, as well as completion of the daily diary (symptom and medication logs) and questionnaires (CAT, BDI/TDI, SGRQ). Vital signs and a physical examination will be performed, and inspiratory flow rate will be determined using the In-Check DIAL. Medications will be adjusted to ensure clinical stability prior to randomization.

Baseline Study Visit 2 occurs within one week of the screening visit. Prior to this visit, participants must not have taken study medication within 48 hours or rescue medication within 6 hours of pulmonary function testing; otherwise, the visit will be rescheduled. At this visit, medical history, current medications, and adverse events are reviewed. Compliance with the daily diary (symptom and medication logs) is assessed, and participants must demonstrate ≥80% completion to continue. Participants complete CAT, BDI, and SGRQ questionnaires, undergo physical examination and vital sign measurement, and perform baseline pulmonary function testing in a plethysmograph. Eligible participants are then randomized 1:1 to receive either active drugs via DPI (Group A) or nebulizer (Group B), with treatment assignments generated using permuted blocks. Group A receives Anoro Ellipta DPI plus nebulized Revefenacin and Formoterol placebos, while Group B receives nebulized Revefenacin and Formoterol plus placebo DPI. The nebulizer is always administered first, followed by the DPI; Time 0 is defined as the end of DPI administration. Post-dose, vital signs and pulmonary function tests are conducted at 1, 2, 4, and 6 hours. Participants also receive training on diary use, study drug/device administration, and medication compliance, and they begin the assigned treatment for 12 weeks with morning and evening doses as per group assignment.

Following Visit 2, patients will continue their assigned treatments twice daily for 12 weeks. Telephone follow-ups will occur at weeks 4 and 8 (Phone Visits 1 and 2) to monitor symptoms, adverse events, and medication adherence, with administration of additional questionnaires.

The final Study Visit 3 will take place at week 12 and will include repeat pulmonary function testing pre-dose and at 1, 2, 4, and 6 hours post-dose, symptom questionnaires, vital signs, and adverse event assessment. Throughout the study, patients will maintain daily symptom diaries, including CAT scores.

• Percentage change in Residual Volume (RV) from baseline after inhalation of LAMA/LABA combination with a nebulizer versus a DPI [Срок оценки: From pre-dose (baseline measurement) to post-dose measurements at 1, 2, 4, and 6 hours during study visit 2 (Week 2) and study visit 3 (Week 12)]
• Percentage change in Total Lung Capacity (TLC) from baseline after inhalation of LAMA/LABA combination with a nebulizer versus a DPI [Срок оценки: From pre-dose (baseline measurement) to post-dose measurements at 1, 2, 4, and 6 hours during study visit 2 (Week 2) and study visit 3 (Week 12)]
• Percentage change in airway resistance (Raw) from baseline after inhalation of LAMA/LABA combination with a nebulizer versus a DPI [Срок оценки: From pre-dose (baseline measurement) to post-dose measurements at 1, 2, 4, and 6 hours during study visit 2 (Week 2) and study visit 3 (Week 12)]
• Maximum percentage change in inspiratory capacity between 0 and 6 hours after LAMA/LABA combination with a nebulizer versus a DPI [Срок оценки: From pre-dose (baseline measurement) to post-dose measurements at 1, 2, 4, and 6 hours during study visit 2 (Week 2) and study visit 3 (Week 12)]
• Maximum percentage change in RV between 0 and 6 hours after LAMA/LABA combination [Срок оценки: From pre-dose (baseline measurement) to post-dose measurements at 1, 2, 4, and 6 hours during study visit 2 (Week 2) and study visit 3 (Week 12)]
• Maximum Percentage Change in Airway Resistance (Raw) between 0 and 6 hours after LAMA/LABA [Срок оценки: From pre-dose (baseline measurement) to post-dose measurements at 1, 2, 4, and 6 hours during study visit 2 (Week 2) and study visit 3 (Week 12)]
• Correlation of peak inspiratory flow rate with peak IC change from baseline [Срок оценки: From pre-dose (baseline measurement) to post-dose measurements at 1, 2, 4, and 6 hours during study visit 2 (Week 2) and study visit 3 (Week 12)]
• Comparison of CAT scores in patients receiving medications with DPI vs nebulizer [Срок оценки: From baseline (Visit 2, Week 2) through study completion (Visit 3, Week 12)]
• Comparison of SGRQ scores in patients receiving medications with DPI vs nebulizer [Срок оценки: At baseline (Visit 2, Week 2), and at study completion (Visit 3, Week 12)]
• Change in TDI in patients receiving medications with DPI vs nebulizer [Срок оценки: Measured at Week 4 (Phone Visit 1), Week 8 (Phone Visit 2), and Week 12 (Study Visit 3)]
• Change in CAT scores in patients receiving medications with DPI vs nebulizer [Срок оценки: From baseline (Visit 2, Week 2) through study completion (Visit 3, Week 12)]
• Change in SGRQ scores in patients receiving medications with DPI vs nebulizer [Срок оценки: Measured at study visit 2 at week 2 and study completion visit 3 at week 12]