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 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).

• Revefenacin (YUPELRI) & Formoterol (Perforomist) (Drug): Revefenacin is a Long-acting anticholinergics (LAMAs) and Formoterol is Long-acting bronchodilators, beta-agonists (LABAs).
• Albuterol Inhalation Aerosol (short-acting beta-agonists) & Ipratropium Aerosol (short-acting anticholinergic) (Drug): Albuterol Inhalation Aerosol (short-acting beta-agonists) \& Ipratropium Aerosol (short-acting anticholinergic)

Primary outcomes

• Difference in Modified Borg Dyspnea Scale Scores Between Groups [From enrollment to the end of treatment at Day 7]: 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.

Secondary outcomes

• 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]

Sex: All, ages: 40 Years to any

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

Participant flow

Outcome results

• Difference in Modified Borg Dyspnea Scale Scores Between Groups (Primary), Least squares mean, scores on a scale: Experimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist) 1.89 (1.34 to 2.45); Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol(Ventolin) as Standard of Care 1.92 (1.37 to 2.46) (p 0.95)
• Total Visits for Study Drug Administration Per Day Received by Each Patient (Secondary), Median, visits: Experimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist) 1.50 (1.00 to 2.00); Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol(Ventolin) as Standard of Care 2.00 (1.50 to 2.50) (p 0.28)
• Total Doses of Bronchodilators Per Hospital Stay (Secondary), Least squares mean, doses: Experimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist) 11.14 (9.34 to 12.94); Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol(Ventolin) as Standard of Care 21.96 (16.03 to 27.89) (p < .001)
• Total Number of Rescue Doses Administered During the Hospital Stay in Patients With Exacerbations of COPD (Secondary), Least squares mean, Dose: Experimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist) 1.25 (0.47 to 2.04); Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol(Ventolin) as Standard of Care 0.43 (-0.07 to 0.92) (p .08)
• Number of Patients Needing to Switch/Change Their Treatment Regimen (Secondary), Count of participants, Participants: Experimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist) 1; Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol(Ventolin) as Standard of Care 1
• Number of Participants With Failure of Treatment (Need for Mechanical Ventilation or Death) (Secondary), Count of participants, Participants: Experimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist) 0; Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol(Ventolin) as Standard of Care 0
• Need for Supplemental Oxygen by Nasal Cannula (L/Min) Among Patients With Exacerbations of COPD (Secondary), Mean, L/min: Experimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist) 2.15 (1.43 to 2.49); Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol(Ventolin) as Standard of Care 2.20 (0.74 to 6.37)

Adverse events

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

Other adverse events by term

• Results publication: 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 Pulm. 2024 Sep 11;2(4):100105. doi: 10.1016/j.chpulm.2024.100105. eCollection 2024 Dec. PMID 42548489

• Study Protocol and Statistical Analysis Plan (PDF, 2020-09-14)