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

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

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.

Study Overview

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

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 Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jennifer Ferris, MSHS; Phone Number: 865-305-7975; Email: jferris@utmck.edu

Study Locations

• United States
  • Tennessee
    • Knoxville, Tennessee, United States, 37920-6999
      • Recruiting
      • University of Tennessee Medical Center
      • Contact: Jennifer Ferris, MSHS; Phone Number: 865-305-7975; Email: jferris@utmck.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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); Revefenacin is a Long-acting anticholinergics (LAMAs) and Formoterol is Long-acting bronchodilators, beta-agonists (LABAs).
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); Albuterol Inhalation Aerosol (short-acting beta-agonists) & Ipratropium Aerosol (short-acting anticholinergic)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Tennessee Graduate School of Medicine
• Collaborators: Mylan Pharmaceuticals Inc

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 9, 2020
• Primary Completion (ANTICIPATED): January 30, 2023
• Study Completion (ANTICIPATED): March 30, 2023

Study Registration Dates

• First Submitted: October 21, 2020
• First Submitted That Met QC Criteria: December 3, 2020
• First Posted (ACTUAL): December 7, 2020

Study Record Updates

• Last Update Posted (ACTUAL): November 15, 2022
• Last Update Submitted That Met QC Criteria: November 13, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Albuterol; Ipratropium; Formoterol Fumarate; Cholinergic Antagonists
• Other Study ID Numbers: UTGSM 4586

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes