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

Phase 4

Recruiting

• Conditions: COPD Exacerbation
• Interventions: Drug: Revefenacin (YUPELRI) & Formoterol (Perforomist); Drug: Albuterol Inhalation Aerosol (short-acting beta-agonists) & Ipratropium Aerosol (short-acting anticholinergic)

• Registration Number: NCT04655170
• Lead Sponsor: University of Tennessee Graduate School of Medicine

Brief 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.

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).

Study Timeline

• Study First Submitted: 2020-10-21
• Study First Submitted QC: 2020-12-03
• Study First Posted: 2020-12-07
• Study Start: 2020-12-09
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-13
• Last Update Posted: 2022-11-15
• Primary Completion: 2023-01-30
• Study Completion: 2023-03-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1: Revefenacin (YUPELRI) & Formoterol (Perforomist)	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.
Group 2: Ipratropium Bromide (Atrovent) & Albuterol (Ventolin) as Standard of Care	Albuterol Inhalation Aerosol (short-acting beta-agonists) & Ipratropium Aerosol (short-acting anticholinergic)	Albuterol and Ipratropium every 6 hours nebulized over the 7-day treatment period or until discharge if prior to day 7.

Primary Outcome Measures

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

Trial Locations

Locations (1)

University of Tennessee Medical Center; 🇺🇸 Knoxville, Tennessee, United States