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)

NCT07721922 | Not Yet Recruiting Phase 4 FDA Drug

• 1 other identifier: 5482
• Study Type: interventional
• Target: 280
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

COPD Exacerbation

Keywords

ECOPD

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• 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)

Study Arms (2)

Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist)

EXPERIMENTAL

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; Drug: formoterol fumarate; Other: Placebo (Sterile Normal Saline)

Group2: Ipratropium Bromide (Atrovent) & Albuterol (Ventolin)

ACTIVE COMPARATOR

Albuterol and Ipratropium every 6 hours nebulized over the 7-day treatment period or until discharge if prior to day 7.

Drug: Albuterol sulfate; Drug: Ipratropium Bromide

Interventions

Revefenacin DRUG

Revefenacin 175 µg in 3 mL inhalation solution administered once daily in the morning via oral inhalation using a jet nebulizer.

Also known as: YUPELRI

Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist)

formoterol fumarate DRUG

Formoterol fumarate 20 μg in 2 mL inhalation solution administered twice daily in the morning and evening via oral inhalation using a jet nebulizer.

Also known as: Perforomist

Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist)

Placebo (Sterile Normal Saline) OTHER

Twice daily (sterile normal saline 3 ml) to maintain blinding and mask the difference in dosing frequency compared with the comparator arm.

Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist)

Albuterol sulfate DRUG

Albuterol sulfate 2.5 mg in 3 mL inhalation solution administered 4 times daily via oral inhalation using a jet nebulizer.

Also known as: Ventolin

Group2: Ipratropium Bromide (Atrovent) & Albuterol (Ventolin)

Ipratropium Bromide DRUG

Ipratropium Bromide 500 μg in 2.5 mL inhalation solution administered 4 times daily via oral inhalation using a jet nebulizer.

Also known as: Atrovent

Group2: Ipratropium Bromide (Atrovent) & Albuterol (Ventolin)

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or Female
• Any Race
• ≥ 40 years of age
• History of COPD based on EMR or confirmed verbally by the patient
• Presenting to the ED with a primary diagnosis of ECOPD or acute respiratory failure with a secondary diagnosis of COPD
• Able to understand and comply with study procedures
• Willingness to sign and date an Informed Consent Form

You may not qualify if:

• Patients unable or unwilling to sign an informed consent or cooperate with study procedures
• Patients who are hypersensitive to Formoterol or Revefenacin
• Patients who are intubated, have tracheotomy, are receiving mechanical ventilation by mask or artificial airway
• Patients who have previously participated in the study
• 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
• 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)
• Patients with a current diagnosis of lung cancer requiring treatment
• Pulmonary diseases other than COPD, or lobar pneumonia
• Patients with acute psychiatric illness deemed significant by the investigator
• Patients with a history of glaucoma deemed significant by the investigator
• History of urinary retention deemed significant by the investigator
• Women who are pregnant or breastfeeding

Sponsors & Collaborators

• University of Tennessee Graduate School of Medicine: lead
• Viatris Inc.: collaborator

Study Sites (1)

University of Tennessee Medical Center

Knoxville, Tennessee, 37920, United States

Location

MeSH Terms

Interventions

revefenacin; Formoterol Fumarate; Albuterol; Ipratropium

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Atropine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Belladonna Alkaloids; Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2026
• First Posted: July 23, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: July 23, 2026

Record last verified: 2026-06

Locations

US (1)