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

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

Official Title
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Randomized, Parallel-group Trial to Evaluate Feasibility, Safety and Efficacy of Nebulized Long-Acting Bronchodilators (Formoterol and Revefenacin) vs. Short-Acting Bronchodilators (Albuterol and Ipratropium) in Hospitalized Patients With AECOPD

Conditions
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COPD Exacerbation

Intervention / Treatment
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* Drug: Revefenacin (YUPELRI) & Formoterol (Perforomist)
* Drug: Albuterol Inhalation Aerosol (short-acting beta-agonists) & Ipratropium Aerosol (short-acting anticholinergic)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or Female Any Race ≥ 40 years of age Admitted to the hospital with a primary diagnosis of AECOPD 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 Exclusion Criteria: 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, in the opinion of the investigators, who are rapidly decompensating and are immediately in need, or will soon need, ventilator support 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 Patients that test positive for COVID-19 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 12 Women who are pregnant or breast feeding

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participating patients with AECOPD will be randomized 1:1 to either a standard bronchodilator protocol with nebulized Albuterol and Ipratropium every 6 hours or nebulized Revefenacin 175 μg once per day and Formoterol 20 μg twice per day. Each patient will have a single randomization number indicating the allocated treatment. The treatment assignments will be generated with the use of a pseudo-random-number generator with stratification for age groups (<50, 50-69, >70) that will be used to ensure balance of these factors in the numbers of subjects assigned to each of the two treatments. The allocation to treatment arms will be according to a predetermined computer-generated randomization schedule that will not be disclosed to the clinical investigators.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist)<br>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)<br>* Revefenacin is a Long-acting anticholinergics (LAMAs) and Formoterol is Long-acting bronchodilators, beta-agonists (LABAs).<br>|
| Active Comparator: Group 2: Ipratropium Bromide (Atrovent) & Albuterol (Ventolin) as Standard of Care<br>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)<br>* Albuterol Inhalation Aerosol (short-acting beta-agonists) & Ipratropium Aerosol (short-acting anticholinergic)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in 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. | change from baseline borg dyspnea score at day 3 | 
| Difference in 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. | change from baseline borg dyspnea score at day 7 | 
| Difference in 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. | change from day 3 borg dyspnea score at day 7 | 
| Difference in the mean total doses of short acting bronchodilators (rescue) used during study participation between each group. | Subject in both groups will be allowed to use standard of care rescue short-acting bronchodilators throughout their study participation. | up to 7 days | 
| The difference in the lowest level of FiO2 employed at each visit between group 1 and group 2 | The lowest level of FiO2 will be recorded from the subjects EMR record at each visit during study participation and the difference between group 1 and group 2 will be noted. | at baseline | 
| The difference in the lowest level of FiO2 employed at each visit between group 1 and group 2 | The lowest level of FiO2 will be recorded from the subjects EMR record at each visit during study participation and the difference between group 1 and group 2 will be noted. | at day 3 | 
| The difference in the lowest level of FiO2 employed at each visit between group 1 and group 2 | The lowest level of FiO2 will be recorded from the subjects EMR record at each visit during study participation and the difference between group 1 and group 2 will be noted. | at day 7 | 
| Number of total subjects that had to stop treatment early between groups | Total percent of patients that had to switch therapy due to lack of response between each group. | Through study completion, up to 7 days | 
| The total number of subjects with Adverse Events, SAE's, ET, and Deaths between groups. | Adverse Events, SAE's, ET, and Deaths will be recorder for every subjects in both groups until the end of their study participation. | Through study completion, up to 7 days |