Feasibility, Safety and Efficacy of Nebulized Long-Acting Bronchodilators (Formoterol and Revefenacin) vs. Short-Acting Bronchodilators (Albuterol and Ipratropium) in Hospitalized Patients With AECOPD

Randomized, Parallel-group Trial to Evaluate Feasibility, Safety and Efficacy of Nebulized Long-Acting Bronchodilators (Formoterol and Revefenacin) vs. Short-Acting Bronchodilators (Albuterol and Ipratropium) in Hospitalized Patients With AECOPD

The purpose of this study is to assess the feasibility, safety and efficacy of a combination of nebulized Formoterol and Revefenacin among patients hospitalized for AECOPD compared with standard-of-care therapy with nebulized Albuterol and Ipratropium.

Study Overview

• Status: Completed
• Conditions: COPD Exacerbation
• Intervention / Treatment: Drug: Revefenacin (YUPELRI) & Formoterol (Perforomist); Drug: Albuterol Inhalation Aerosol (short-acting beta-agonists) & Ipratropium Aerosol (short-acting anticholinergic)

Detailed Description

A prospective, parallel group, randomized clinical trial in 60 patients hospitalized with the primary diagnosis of AECOPD or acute respiratory failure with a secondary diagnosis of COPD (ICD-10 codes J44.1 and J96 - J96.2 with J44.9).

The plan is to:

Administer standard bronchodilator protocol with nebulized Albuterol and Ipratropium every 6 hours (n=30)

versus

Nebulized Revefenacin 175 μg once per day and Formoterol 20 μg twice per day (n=30) for up to 7 days of treatment. Study medication will be administered by standard jet nebulizers in both groups.

Investigators will:

• Collect the Borg dyspnea scale twice a day during hospitalization
• Record the total doses of bronchodilators per day received by each patient
• Record the number of rescue doses needed per day of hospital stay
• Record the lowest level of FiO2 employed on days 1, 3 and 7 of hospital stay
• Record all adverse events and concurrent medications

Investigators will collect:

Physical Exam (Day 1, 3, 7, or ET) Serum Chemistry (Day 1, 3, 7, or ET) Hematology (Day 1, 3, 7, or ET) Chest X-Ray (Day 1).

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Knoxville, Tennessee, United States, 37920-6999
      • University of Tennessee Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or Female
2. Any Race
3. ≥ 40 years of age
4. Admitted to the hospital with a primary diagnosis of AECOPD or acute respiratory failure with a secondary diagnosis of COPD
5. Able to understand and comply with study procedures
6. Willingness to sign and date an Informed Consent Form

Exclusion Criteria:

1. Patients unable or unwilling to sign an informed consent or cooperate with study procedures
2. Patients who are hypersensitive to Formoterol or Revefenacin
3. Patients who are intubated, have tracheotomy, are receiving mechanical ventilation by mask or artificial airway
4. Patients, in the opinion of the investigators, who are rapidly decompensating and are immediately in need, or will soon need, ventilator support
5. Patients who, per the investigator, have unstable cardiovascular disease (e.g., uncontrolled, hypertension, unstable angina, recent MI (within 12 weeks), ventricular arrhythmia, or decompensated heart failure)
6. Patients with a current diagnosis of lung cancer requiring treatment
7. Patients that test positive for COVID-19
8. Pulmonary diseases other than COPD, or lobar pneumonia
9. Patients with acute psychiatric illness deemed significant by the investigator
10. Patients with a history of glaucoma deemed significant by the investigator
11. History of urinary retention deemed significant by the investigator

12 Women who are pregnant or breast feeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist); Revefenacin 175 μg once per day and Formoterol 20 μg twice per day via jet nebulizer for 7 days or until discharge if prior to day 7.	Drug: Revefenacin (YUPELRI) & Formoterol (Perforomist); Revefenacin is a Long-acting anticholinergics (LAMAs) and Formoterol is Long-acting bronchodilators, beta-agonists (LABAs).
Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol (Ventolin) as Standard of Care; Albuterol and Ipratropium every 6 hours nebulized over the 7-day treatment period or until discharge if prior to day 7.	Drug: Albuterol Inhalation Aerosol (short-acting beta-agonists) & Ipratropium Aerosol (short-acting anticholinergic); Albuterol Inhalation Aerosol (short-acting beta-agonists) & Ipratropium Aerosol (short-acting anticholinergic)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in Modified Borg Dyspnea Scale Scores Between Groups	The Modified Borg Dyspnea Scale asks the subject to rate the difficulty of their breathing. It starts at number 0 where breathing is causing no difficulty at all and progresses through to number 10 where breathing difficulty is maximal. This scale was recorded prior to dosing twice a day between 7 and 9 am & pm.	From enrollment to the end of treatment at Day 7

Secondary Outcome Measures

Outcome Measure	Time Frame
Total Visits for Study Drug Administration Per Day Received by Each Patient	From enrollment to the end of treatment at Day 7
Total Doses of Bronchodilators Per Hospital Stay	From enrollment to the end of treatment at Day 7
Total Number of Rescue Doses Administered During the Hospital Stay in Patients With Exacerbations of COPD	From enrollment to the end of treatment at Day 7
Number of Patients Needing to Switch/Change Their Treatment Regimen	From enrollment to the end of treatment at Day 7
Number of Participants With Failure of Treatment (Need for Mechanical Ventilation or Death)	From enrollment to the end of treatment at Day 7
Need for Supplemental Oxygen by Nasal Cannula (L/Min) Among Patients With Exacerbations of COPD	Days 1 and 3

Collaborators and Investigators

• Sponsor: University of Tennessee Graduate School of Medicine
• Collaborators: Mylan Pharmaceuticals Inc

Publications and helpful links

General Publications

• Dhand R, Treat S, Ferris J, Terry PD, Walker T, Elder S, Church D, Dennis D, Faircloth B, Onar G, Heidel RE, Biney I, Valdes M, Bhagat M, Fuerst N, Cusick S. Safety, Efficacy, and Feasibility of Nebulized Long-Acting Bronchodilators vs Short-Acting Bronchodilators in Hospitalized Patients With Acute Exacerbations of COPD: A Phase IV, Randomized, Parallel-Group Clinical Trial. CHEST Pulmonary. 2024 Dec;2(4):100105

Helpful Links

• Results Publication Link

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2020
• Primary Completion (Actual): January 19, 2023
• Study Completion (Actual): June 1, 2023

Study Registration Dates

• First Submitted: October 21, 2020
• First Submitted That Met QC Criteria: December 3, 2020
• First Posted (Actual): December 7, 2020

Study Record Updates

• Last Update Posted (Actual): August 3, 2026
• Last Update Submitted That Met QC Criteria: July 14, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Amines; Alcohols; Amino Alcohols; Ethanolamines; Formoterol Fumarate; revefenacin
• Other Study ID Numbers: UTGSM 4586

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes