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)

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

Overview

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.

Interventions

• Drug Revefenacin
  Revefenacin 175 µg in 3 mL inhalation solution administered once daily in the morning via oral inhalation using a jet nebulizer.
• Drug formoterol fumarate
  Formoterol fumarate 20 μg in 2 mL inhalation solution administered twice daily in the morning and evening via oral inhalation using a jet nebulizer.
• Other 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.
• Drug Albuterol sulfate
  Albuterol sulfate 2.5 mg in 3 mL inhalation solution administered 4 times daily via oral inhalation using a jet nebulizer.
• Drug Ipratropium Bromide
  Ipratropium Bromide 500 μg in 2.5 mL inhalation solution administered 4 times daily via oral inhalation using a jet nebulizer.

Primary outcome measures

• Difference in Modified Borg Dyspnea Scale scores between groups [Time frame: From enrollment through Day 7 (end of treatment)]

Secondary outcome measures (9)

• 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)]

Eligibility criteria

Inclusion criteria

• 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

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 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:

i. Inability to maintain respiratory effort ii. Cyanosis iii. Hemodynamic instability iv. Deterioration in mental status

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

United States · 1 center

• University of Tennessee Medical Center — Knoxville

Identifiers

NCT: NCT07721922 · 5482

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗