COPD ExacerbationPhase 4NCT07721922
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 4 study testing Revefenacin, formoterol fumarate and Albuterol sulfate in people with COPD Exacerbation, run by University of Tennessee Graduate School of Medicine at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- COPD Exacerbation
- What is being tested?
- Revefenacin, formoterol fumarate and Albuterol sulfate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 280 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Nov 2026to 1 Sep 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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:
- Inability to maintain respiratory effort ii. Cyanosis iii. Hemodynamic instability iv. Deterioration in mental status
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
University of Tennessee Medical Center
Knoxville, Tennessee, 37920
Jennifer Ferris, MSHS, 865-305-7975, jferris@utmck.edu
About this study
Official title: 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.
- Conditions
- COPD Exacerbation
- Being tested
- Revefenacin, formoterol fumarate, Placebo (Sterile Normal Saline), Albuterol sulfate, Ipratropium Bromide
- Keywords
- ECOPD
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RevefenacinDrug
Also called YUPELRI
Revefenacin 175 µg in 3 mL inhalation solution administered once daily in the morning via oral inhalation using a jet nebulizer.
formoterol fumarateDrug
Also called Perforomist
Formoterol fumarate 20 μg in 2 mL inhalation solution administered twice daily in the morning and evening via oral inhalation using a jet nebulizer.
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.
Albuterol sulfateDrug
Also called Ventolin
Albuterol sulfate 2.5 mg in 3 mL inhalation solution administered 4 times daily via oral inhalation using a jet nebulizer.
Ipratropium BromideDrug
Also called Atrovent
Ipratropium Bromide 500 μg in 2.5 mL inhalation solution administered 4 times daily via oral inhalation using a jet nebulizer.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Albuterol sulfate; Drug: Ipratropium Bromide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From enrollment through Day 7 (end of treatment)
Secondary outcomes (9)
Number of patients discharged home from the ED
Measured: 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)
Measured: From enrollment through Day 7 (end of treatment)
Length of hospital or ED stay
Measured: From enrollment through Day 7 (end of treatment)
Number of Participants with the Need to Switch Therapy
Measured: From enrollment through Day 7 (end of treatment)
Total number of bronchodilator doses per hospital or ED stay
Measured: From enrollment through Day 7 (end of treatment)
Total number of rescue doses used
Measured: 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.
Measured: From enrollment through Day 7 (end of treatment)
Number of Participants Requiring Supplemental Oxygen
Measured: 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.
Measured: From enrollment through Day 7 (end of treatment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2026
- Study start12 Nov 2026 (estimated)
- Primary completion1 Sep 2028 (estimated)
- Study completion1 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COPD ExacerbationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 280 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Tennessee Graduate School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Viatris Inc.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07721922
- Sponsor's protocol ID
- 5482
- Status last verified
- Jun 2026
- First submitted
- 23 Jun 2026
- Last updated
- 19 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07721922
- Acronym / sponsor ID
- 5482
- Conditions
- COPD Exacerbation
- Keywords
- ECOPD
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 280 participants (estimated)
- Lead sponsor
- University of Tennessee Graduate School of MedicineUniversity, hospital or other
- Collaborators
- Viatris Inc.
- Study start
- 12 Nov 2026 (estimated)
- Primary completion
- 1 Sep 2028 (estimated)
- Study completion
- 1 Sep 2028 (estimated)
- First posted
- 23 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist) | Experimental | Drug: Revefenacin, Drug: formoterol fumarate, Other: Placebo (Sterile Normal Saline)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. |
| Group2: Ipratropium Bromide (Atrovent) & Albuterol (Ventolin) | Active comparator | Drug: Albuterol sulfate, Drug: Ipratropium BromideAlbuterol and Ipratropium every 6 hours nebulized over the 7-day treatment period or until discharge if prior to day 7. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (13 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RevefenacinAlso: YUPELRIRevefenacin 175 µg in 3 mL inhalation solution administered once daily in the morning via oral inhalation using a jet nebulizer. | Drug | Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist) |
| formoterol fumarateAlso: PerforomistFormoterol fumarate 20 μg in 2 mL inhalation solution administered twice daily in the morning and evening via oral inhalation using a jet nebulizer. | Drug | Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist) |
| 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. | Other | Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist) |
| Albuterol sulfateAlso: VentolinAlbuterol sulfate 2.5 mg in 3 mL inhalation solution administered 4 times daily via oral inhalation using a jet nebulizer. | Drug | Group2: Ipratropium Bromide (Atrovent) & Albuterol (Ventolin) |
| Ipratropium BromideAlso: AtroventIpratropium Bromide 500 μg in 2.5 mL inhalation solution administered 4 times daily via oral inhalation using a jet nebulizer. | Drug | Group2: Ipratropium Bromide (Atrovent) & Albuterol (Ventolin) |
Primary outcome
Difference in Modified Borg Dyspnea Scale scores between groups
Time frame: From enrollment through Day 7 (end of treatment)
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.
9 secondary outcomes
Number of patients discharged home from the ED
Time frame: 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)
Time frame: From enrollment through Day 7 (end of treatment)
Length of hospital or ED stay
Time frame: From enrollment through Day 7 (end of treatment)
Number of Participants with the Need to Switch Therapy
Time frame: From enrollment through Day 7 (end of treatment)
Total number of bronchodilator doses per hospital or ED stay
Time frame: From enrollment through Day 7 (end of treatment)
Total number of rescue doses used
Time frame: From enrollment through Day 7 (end of treatment)
Number of Participants with Failure of Treatment (Need for Mechanical Ventilation or Death
Time frame: From enrollment through Day 7 (end of treatment)
Number of Participants Requiring Supplemental Oxygen
Time frame: From enrollment through Day 7 (end of treatment)
Differences in FEV1/FVC values between enrollment and discharge/end of study.
Time frame: From enrollment through Day 7 (end of treatment)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Revefenacin, formoterol fumarate and Albuterol sulfate in people with COPD Exacerbation, run by University of Tennessee Graduate School of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 19 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in Modified Borg Dyspnea Scale scores between groups (time frame: From enrollment through Day 7 (end of treatment)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2026.