Efficacy of Nebulized Long-Acting Bronchodilators (Formoterol and Revefenacin) vs. Short-Acting Bronchodilators (Albuterol and Ipratropium) in Patients Presenting to the Emergency Department With Acute Exacerbation of COPD (ECOPD)

Efficacy of Nebulized Long-Acting Bronchodilators (Formoterol and Revefenacin) vs. Short-Acting Bronchodilators (Albuterol and Ipratropium) in Patients Presenting to the Emergency Department With Acute Exacerbation of COPD (ECOPD): A Phase IV, Prospective, Randomized, Blinded, Parallel-group Trial

The primary aim is to determine whether nebulized Formoterol twice daily plus Revefenacin once daily is non-inferior to standard-of-care nebulized Albuterol and Ipratropium therapy four times daily in relieving dyspnea among patients with ECOPD presenting to the ED and requiring hospitalization, as measured by the Modified Borg Dyspnea Scale.

The hypothesize is that patients in the ED for ECOPD, improvement in symptoms, safety, and length of ED or hospital stay after treatment with nebulized Revefenacin and Formoterol will be non-inferior to the Albuterol and Ipratropium combination. The long-acting bronchodilator regimen will provide comparable symptom control with fewer total drug doses compared with standard treatment with short-acting bronchodilators, namely, nebulized Albuterol and Ipratropium. To the best of our knowledge, this will be the first prospective, randomized, double-blind investigation to compare a combination of long-acting nebulized LAMA/LABA bronchodilators with a standard-of-care combination of short-acting nebulized SAMA/SABA bronchodilators in patients with an ECOPD in the ED/hospital setting.

Study Overview

• Status: Not yet recruiting
• Conditions: COPD Exacerbation
• Intervention / Treatment: Drug: Revefenacin; Drug: formoterol fumarate; Other: Placebo (Sterile Normal Saline); Drug: Albuterol sulfate; Drug: Ipratropium Bromide

• Study Type: Interventional
• Enrollment (Estimated): 280
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee Medical Center
      • Contact: Jennifer Ferris, MSHS; Phone Number: 865-305-7975; Email: jferris@utmck.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or Female
2. Any Race
3. ≥ 40 years of age
4. History of COPD based on EMR or confirmed verbally by the patient
5. Presenting to the ED with a primary diagnosis of ECOPD or acute respiratory failure with a secondary diagnosis of COPD
6. Able to understand and comply with study procedures
7. 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 who have previously participated in the study

5. Patients, in the opinion of the investigators, who are rapidly decompensating and are immediately in need, or will soon need, ventilator support based on:

   i. Inability to maintain respiratory effort ii. Cyanosis iii. Hemodynamic instability iv. Deterioration in mental status

6. 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)
7. Patients with a current diagnosis of lung cancer requiring treatment
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 breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist); Participants will receive Revefenacin 175 µg once daily and Formoterol 20 µg twice daily via a jet nebulizer for up to 7 days or until hospital discharge (if discharge occurs before Day 7). Participants will also receive placebo (sterile normal saline) to maintain blinding and mask the difference in dosing frequency compared with the comparator arm.	Drug: Revefenacin; Revefenacin 175 µg in 3 mL inhalation solution administered once daily in the morning via oral inhalation using a jet nebulizer.; Other Names: YUPELRI; Drug: formoterol fumarate; Formoterol fumarate 20 μg in 2 mL inhalation solution administered twice daily in the morning and evening via oral inhalation using a jet nebulizer.; Other Names: Perforomist; Other: Placebo (Sterile Normal Saline); Twice daily (sterile normal saline 3 ml) to maintain blinding and mask the difference in dosing frequency compared with the comparator arm.
Active Comparator: Group2: Ipratropium Bromide (Atrovent) & Albuterol (Ventolin); Albuterol and Ipratropium every 6 hours nebulized over the 7-day treatment period or until discharge if prior to day 7.	Drug: Albuterol sulfate; Albuterol sulfate 2.5 mg in 3 mL inhalation solution administered 4 times daily via oral inhalation using a jet nebulizer.; Other Names: Ventolin; Drug: Ipratropium Bromide; Ipratropium Bromide 500 μg in 2.5 mL inhalation solution administered 4 times daily via oral inhalation using a jet nebulizer.; Other Names: Atrovent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in Modified Borg Dyspnea Scale scores between groups	This is a 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 will be recorded prior to dosing twice a day between 7 and 9 am & pm. Scores from Group 1 and Group 2 will be averaged and compared.	From enrollment through Day 7 (end of treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients discharged home from the ED		From enrollment through Day 7 (end of treatment)
Number of patients admitted to a hospital floor or require ED observation for >24 hours (in-hospital patients)		From enrollment through Day 7 (end of treatment)
Length of hospital or ED stay		From enrollment through Day 7 (end of treatment)
Number of Participants with the Need to Switch Therapy		From enrollment through Day 7 (end of treatment)
Total number of bronchodilator doses per hospital or ED stay		From enrollment through Day 7 (end of treatment)
Total number of rescue doses used		From enrollment through Day 7 (end of treatment)
Number of Participants with Failure of Treatment (Need for Mechanical Ventilation or Death	Failure of treatment will be defined as any of the following: death, the need for a patient to receive mechanical ventilation, or the need for a patient to discontinue long-acting bronchodilators during the trial. The need for rescue medications while maintaining the assigned treatment will not be considered a failure of treatment.	From enrollment through Day 7 (end of treatment)
Number of Participants Requiring Supplemental Oxygen		From enrollment through Day 7 (end of treatment)
Differences in FEV1/FVC values between enrollment and discharge/end of study.	Bedside spirometry will be performed by respiratory therapists with the patient in a sitting position using a handheld portable spirometer. The patient will be asked to make a tight seal around the mouthpiece with their lips and forcefully exhale after a deep inhalation. The patient will be instructed to continue forceful and rapid exhalation until no more air is expelled from their lungs. The best of 3 efforts will be used for analysis. FEV1/FVC<0.7 will be used to diagnose airflow obstruction.	From enrollment through Day 7 (end of treatment)

Collaborators and Investigators

• Sponsor: University of Tennessee Graduate School of Medicine
• Collaborators: Viatris Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: June 23, 2026
• First Submitted That Met QC Criteria: July 20, 2026
• First Posted (Actual): July 23, 2026

Study Record Updates

• Last Update Posted (Actual): July 23, 2026
• Last Update Submitted That Met QC Criteria: July 20, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: ECOPD
• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds; Alkaloids; Amines; Alcohols; Aza Compounds; Amino Alcohols; Ethanolamines; Phenethylamines; Ethylamines; Heterocyclic Compounds, Bridged-Ring; Atropine Derivatives; Tropanes; Azabicyclo Compounds; Belladonna Alkaloids; Solanaceous Alkaloids; Bridged Bicyclo Compounds, Heterocyclic; Formoterol Fumarate; Albuterol; Ipratropium; revefenacin
• Other Study ID Numbers: 5482

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No