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

NCT ID: NCT07133880

Last Updated: 2025-08-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-12-05
• Study Completion Date: 2025-12-01

Brief Summary

The purpose of this study is to compare the effectiveness of inhaled bronchodilators delivered via nebulizers vs. dry powder inhalers (DPIs) in symptomatic participants with Chronic Obstructive Pulmonary Disease (COPD) who have airflow obstruction (FEV1/FVC ≤ 70%) and show significant air trapping (RV ≥ 120% of predicted).

The investigators hypothesize that, in patients with symptomatic COPD, therapy with a long-acting anti muscarinic agent/long-acting beta agonist (LAMA/LABA) combination administered by nebulizer will improve hyperinflation (increase in inspiratory capacity and reduction in residual volume) and reduce symptoms related to COPD to a greater extent than LAMA/LABA therapy given by a DPI.

The study aims to demonstrate the following:

1. Compare the values of inspiratory capacity (IC) and residual volume (RV) in patients receiving LAMA/LABA by DPI with those receiving LAMA/LABA by nebulizer

2. Compare patient reported outcomes (COPD Assessment Test (CAT score), Baseline/Transition Dyspnea Index (BDI/TDI) and the St. George Respiratory Questionnaire (SGRQ) in symptomatic patients with COPD receiving LAMA/LABA by DPI with those receiving LAMA/LABA by nebulizer

Detailed Description

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.

Conditions

COPD (Chronic Obstructive Pulmonary Disease)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

DPI Treatment Group

Group A: Receives Umeclidinium 62.5 µg and Vilanterol 25 µg via DPI and Revefenacin placebo and formoterol placebo (sterile normal saline) via nebulizer at treatment visit # 2 and will continue with assigned treatment and placebo for 12 weeks

Group Type: ACTIVE_COMPARATOR

umeclidinium 62.5 µg and vilanterol 25 µg

Intervention Type: DRUG

DPI Treatment

Placebo ( Revefenacin and Formoterol )

Intervention Type: DRUG

Placebo Nebulizer Treatment

Nebulizer Treatment Group

Group B: Receives revefenacin 175 µg and formoterol 20 µg via nebulizer and placebo DPI at treatment visit # 2 and will continue with assigned treatment and placebo for 12 weeks

Group Type: ACTIVE_COMPARATOR

Revefenacin 175 µg, Formoterol 20 µg

Intervention Type: DRUG

Nebulizer Treatment

Placebo DPI

Intervention Type: DRUG

Placebo DPI Treatment

Interventions

umeclidinium 62.5 µg and vilanterol 25 µg

DPI Treatment

Intervention Type: DRUG

Revefenacin 175 µg, Formoterol 20 µg

Nebulizer Treatment

Intervention Type: DRUG

Placebo ( Revefenacin and Formoterol )

Placebo Nebulizer Treatment

Intervention Type: DRUG

Placebo DPI

Placebo DPI Treatment

Intervention Type: DRUG

Other Intervention Names

Anoro Ellipta; Yupelri; Perforomist; Normal Saline

Eligibility Criteria

Inclusion Criteria

1. Age > 40 years

2. Either sex

3. Current smoker or past cigarette smoking history of > 10 pack-years

4. Symptoms of COPD (cough, sputum production, shortness of breath)

5. Modified Medical Research Council Dyspnea Scale (mMRC) score ≥2 or CAT score ≥10 at Screening/Run-in visit

6. A PIFR > 30 at screening

7. FEV1/FVC ratio < 70% (within the past 12 months)

8. Residual volume (RV) ≥ 120% predicted (within the past 12 months

Exclusion Criteria

1. Diagnosis of asthma (Verification via medical record and/or patient report)

2. Previously diagnosed atrial fibrillation with rapid ventricular response (heart rate > 110 bpm) or ventricular arrhythmia (ventricular tachycardia) (Verification via medical record and/or patient report)

3. Acute myocardial infarction within 12 weeks of patient study registration (Verification via medical record and/or patient report)

4. Acute exacerbation of congestive heart failure (Verification via medical record and/or patient report)

5. Acute exacerbation of COPD within 8 weeks (Verification via medical record and/or patient report)

6. Recent (within 8 weeks) h/o eye surgery (Verification via medical record and/or patient report)

7. Uncontrolled glaucoma (Verification via medical record and/or patient report)

8. Known diagnosis of liver cirrhosis (Verification via medical record and/or patient report)

9. Known diagnosis of chronic renal insufficiency (defined as a previous serum creatinine > 2.5 mg/dL - Verification via medical record and/or patient report)

10. Intolerance to any of the study drugs

11. Patients receiving long-term azithromycin

12. Planned surgery requiring hospital admission within 3 months

13. Currently enrolled in a pulmonary rehabilitation program

14. Inability to give informed consent

15. Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception (i.e., oral contraceptives, intrauterine devices, diaphragm, or subdermal implants)

16. Inability to understand instructions or comply with the study protocol

17. Participation in another investigational drug clinical trial within 30 days of patient study registration

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Theravance Biopharma

INDUSTRY

Sponsor Role: collaborator

University of Tennessee Graduate School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

The University of Tennessee Graduate School of Medicine

Knoxville, Tennessee, United States

Site Status: RECRUITING

Countries

United States

Facility Contacts

Tracy Walker, Study Coordinator

Role: primary

twalker5@utmck.edu

865-305-4297

Provided Documents

Document Type: Study Protocol

View Document

Other Identifiers

Institutional Review Board

Identifier Type: OTHER

Identifier Source: secondary_id

4889

Identifier Type: -

Identifier Source: org_study_id