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CompletedNCT04655170Updated Aug 3, 2026Results posted

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

A Phase 4 interventional study of Revefenacin (YUPELRI) & Formoterol (Perforomist) and Albuterol Inhalation Aerosol (short-acting beta-agonists) & Ipratropium Aerosol (short-acting anticholinergic) in COPD Exacerbation, sponsored by University of Tennessee Graduate School of Medicine. Completed at 1 site in United States. Open to participants aged 40 Years and older. Per ClinicalTrials.gov, last updated 2026-08-03.

Sponsored by University of Tennessee Graduate School of Medicine · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
60
Allocation
Randomized
Ages
40 Years and older
Sex
All
01

Study summary

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.

Read the 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).

02

Conditions studied

  • COPD Exacerbation
03

In context

Lead sponsor

University of Tennessee Graduate School of Medicine is the lead sponsor of 26 studies on the registry; 13 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
40 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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

05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
60 participants (actual)

Study arms

  • 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)

  • 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)

Interventions

  • DrugRevefenacin (YUPELRI) & Formoterol (Perforomist)

    Revefenacin is a Long-acting anticholinergics (LAMAs) and Formoterol is Long-acting bronchodilators, beta-agonists (LABAs).

  • DrugAlbuterol Inhalation Aerosol (short-acting beta-agonists) & Ipratropium Aerosol (short-acting anticholinergic)

    Albuterol Inhalation Aerosol (short-acting beta-agonists) \& Ipratropium Aerosol (short-acting anticholinergic)

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: From enrollment to the end of treatment at Day 7

Secondary outcomes

  1. Total Visits for Study Drug Administration Per Day Received by Each Patient

    Time frame: From enrollment to the end of treatment at Day 7

  2. Total Doses of Bronchodilators Per Hospital Stay

    Time frame: From enrollment to the end of treatment at Day 7

  3. Total Number of Rescue Doses Administered During the Hospital Stay in Patients With Exacerbations of COPD

    Time frame: From enrollment to the end of treatment at Day 7

  4. Number of Patients Needing to Switch/Change Their Treatment Regimen

    Time frame: From enrollment to the end of treatment at Day 7

  5. Number of Participants With Failure of Treatment (Need for Mechanical Ventilation or Death)

    Time frame: From enrollment to the end of treatment at Day 7

  6. Need for Supplemental Oxygen by Nasal Cannula (L/Min) Among Patients With Exacerbations of COPD

    Time frame: Days 1 and 3

07

Results

Posted Aug 3, 2026

Participant flow

Participant flow — Overall Study
MilestoneExperimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist)Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol(Ventolin) as Standard of Care
Started3030
Completed3030
Not completed00

Outcome measures

PrimaryDifference 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.

Time frame:
From enrollment to the end of treatment at Day 7
Reported as:
Least squares mean · scores on a scale
Difference in Modified Borg Dyspnea Scale Scores Between Groups
scores on a scaleExperimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist)Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol(Ventolin) as Standard of Care
Difference in Modified Borg Dyspnea Scale Scores Between Groups1.89 (1.34 to 2.45)1.92 (1.37 to 2.46)
Statistical analysis
  • Experimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist) vs Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol(Ventolin) as Standard of Care · Generalized Estimating Equations · p = 0.95
SecondaryTotal Visits for Study Drug Administration Per Day Received by Each Patient
Time frame:
From enrollment to the end of treatment at Day 7
Reported as:
Median · visits
Total Visits for Study Drug Administration Per Day Received by Each Patient
visitsExperimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist)Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol(Ventolin) as Standard of Care
Day 11.50 (1.00 to 2.00)2.00 (1.50 to 2.50)
Day 22.00 (2.00 to 2.00)4.00 (3.00 to 5.00)
Day 32.00 (1.50 to 2.50)3.00 (2.00 to 4.00)
Day 42.00 (1.50 to 2.50)3.50 (2.00 to 5.00)
Day 52.00 (2.00 to 2.00)4.00 (3.50 to 4.50)
Day 62.00 (1.625 to 2.375)4.00 (2.75 to 5.25)
Day 72.00 (2.00 to 2.00)4.00 (4.00 to 4.00)
Statistical analysis
  • Experimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist) vs Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol(Ventolin) as Standard of Care · Wilcoxon (Mann-Whitney) · p = 0.28 (This corresponds to Day 1)P values obtained by the Mann-Whitney U test. Statistical significance was assumed at an alpha level of 0.05
  • Experimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist) vs Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol(Ventolin) as Standard of Care · Wilcoxon (Mann-Whitney) · p = < .001 (This corresponds to Day 2)P values obtained by the Mann-Whitney U test. Statistical significance was assumed at an alpha level of 0.05
  • Experimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist) vs Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol(Ventolin) as Standard of Care · Wilcoxon (Mann-Whitney) · p = .001 (This corresponds to Day 3)P values obtained by the Mann-Whitney U test. Statistical significance was assumed at an alpha level of 0.05
  • Experimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist) vs Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol(Ventolin) as Standard of Care · Wilcoxon (Mann-Whitney) · p = .08 (This corresponds to Day 4)P values obtained by the Mann-Whitney U test. Statistical significance was assumed at an alpha level of 0.05
  • Experimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist) vs Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol(Ventolin) as Standard of Care · Wilcoxon (Mann-Whitney) · p = < .001 (This corresponds to Day 5)P values obtained by the Mann-Whitney U test. Statistical significance was assumed at an alpha level of 0.05
  • Experimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist) vs Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol(Ventolin) as Standard of Care · Wilcoxon (Mann-Whitney) · p = .07 (This corresponds to Day 6)P values obtained by the Mann-Whitney U test. Statistical significance was assumed at an alpha level of 0.05
  • Experimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist) vs Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol(Ventolin) as Standard of Care · Wilcoxon (Mann-Whitney) · p = .10 (This corresponds to Day 7)P values obtained by the Mann-Whitney U test. Statistical significance was assumed at an alpha level of 0.05
SecondaryTotal Doses of Bronchodilators Per Hospital Stay
Time frame:
From enrollment to the end of treatment at Day 7
Reported as:
Least squares mean · doses
Total Doses of Bronchodilators Per Hospital Stay
dosesExperimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist)Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol(Ventolin) as Standard of Care
Total Doses of Bronchodilators Per Hospital Stay11.14 (9.34 to 12.94)21.96 (16.03 to 27.89)
Statistical analysis
  • Experimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist) vs Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol(Ventolin) as Standard of Care · Generalized estimating equations · p = < .001
SecondaryTotal Number of Rescue Doses Administered During the Hospital Stay in Patients With Exacerbations of COPD
Time frame:
From enrollment to the end of treatment at Day 7
Reported as:
Least squares mean · Dose
Total Number of Rescue Doses Administered During the Hospital Stay in Patients With Exacerbations of COPD
DoseExperimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist)Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol(Ventolin) as Standard of Care
Total Number of Rescue Doses Administered During the Hospital Stay in Patients With Exacerbations of COPD1.25 (0.47 to 2.04)0.43 (-0.07 to 0.92)
Statistical analysis
  • Experimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist) vs Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol(Ventolin) as Standard of Care · Generalized estimating equations · p = .08
SecondaryNumber of Patients Needing to Switch/Change Their Treatment Regimen
Time frame:
From enrollment to the end of treatment at Day 7
Reported as:
Count of participants · Participants
Number of Patients Needing to Switch/Change Their Treatment Regimen
ParticipantsExperimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist)Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol(Ventolin) as Standard of Care
Number of Patients Needing to Switch/Change Their Treatment Regimen11
SecondaryNumber of Participants With Failure of Treatment (Need for Mechanical Ventilation or Death)
Time frame:
From enrollment to the end of treatment at Day 7
Reported as:
Count of participants · Participants
Number of Participants With Failure of Treatment (Need for Mechanical Ventilation or Death)
ParticipantsExperimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist)Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol(Ventolin) as Standard of Care
Number of Participants With Failure of Treatment (Need for Mechanical Ventilation or Death)00
SecondaryNeed for Supplemental Oxygen by Nasal Cannula (L/Min) Among Patients With Exacerbations of COPD
Time frame:
Days 1 and 3
Reported as:
Mean · L/min
Need for Supplemental Oxygen by Nasal Cannula (L/Min) Among Patients With Exacerbations of COPD
L/minExperimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist)Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol(Ventolin) as Standard of Care
Day 12.15 ± 1.782.20 ± 1.69
Day 31.66 ± 1.451.82 ± 1.28

Adverse events

Collected over From enrollment to the end of treatment at Day 7. Non-serious events are listed at a 1% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Experimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist)0/30 (0%)0/30 (0%)0/30 (0%)
Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol(Ventolin) as Standard of Care0/30 (0%)0/30 (0%)1/30 (3.3%)
Most frequent other events
Most frequent other events
EventExperimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist)Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol(Ventolin) as Standard of Care
Oxygen desaturationRespiratory, thoracic and mediastinal disorders0/301/30

Baseline characteristics

Age, Continuous
Age, Continuous(years)Experimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist)Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol(Ventolin) as Standard of CareTotal
Mean61.8 ± 9.5164.5 ± 9.0563.2 ± 9.30
Sex: Female, Male
Sex: Female, Male(Participants)Experimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist)Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol(Ventolin) as Standard of CareTotal
Female121325
Male181735
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Experimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist)Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol(Ventolin) as Standard of CareTotal
White262854
Black325
Non-White Hispanic/Asian101
Smoking status
Smoking status(Participants)Experimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist)Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol(Ventolin) as Standard of CareTotal
Active tobacco use201939
Previous tobacco use10919
Does not smoke022
CCI Score
CCI Score(Scores on a scale)Experimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist)Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol(Ventolin) as Standard of CareTotal
Mean4.7 ± 2.594.7 ± 2.204.7 ± 2.38
CCI estimated 10-y survival %
CCI estimated 10-y survival %(Percentage)Experimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist)Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol(Ventolin) as Standard of CareTotal
Mean43.9 ± 37.1640.8 ± 35.1442.3 ± 35.89
Comorbidity according to CCI score
Comorbidity according to CCI score(Participants)Experimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist)Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol(Ventolin) as Standard of CareTotal
No comorbidity (score ≤ 1)303
Mild comorbidity (score2)358
High comorbidity (score ≥ 3)242549
No. of comorbid diseases
No. of comorbid diseases(Participants)Experimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist)Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol(Ventolin) as Standard of CareTotal
At least 3 diseases336
4-7 diseases13518
8-11 diseases51116
≥ 12 diseases91120
08

Study locations

1 site
  • University of Tennessee Medical Center
    Knoxville, Tennessee 37920-6999, United States
09

References and documents

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

Study documents

  • Protocol and statistical analysis plan · Sep 14, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Undecided

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 3, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04655170
Lead sponsor
University of Tennessee Graduate School of Medicine
Collaborators
Mylan Pharmaceuticals Inc
Responsible party
Sponsor
First posted
Dec 7, 2020
Start date
Dec 9, 2020
Primary completion
Jan 19, 2023
Completion
Jun 1, 2023
Results posted
Aug 3, 2026
Last update
Aug 3, 2026

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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