Revefenacin in Acute Respiratory Insufficiency in COPD

Study Overview
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Brief Summary
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RARICO is a pragmatic, randomized, controlled, double-blinded, multi-center trial evaluating the safety and feasibility of nebulized revefenacin in comparison to nebulized ipratropium in patients with COPD and acute respiratory failure requiring invasive mechanical ventilation.

Detailed Description
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Objective: To assess the efficacy of nebulized revefenacin in improving the lung mechanics of COPD patients with acute respiratory failure requiring invasive mechanical ventilation (MV), in comparison to a control group receiving the short-acting muscarinic antagonist ipratropium. Hypothesis: Revefenacin is as efficacious as ipratropium in improving the lung mechanics of COPD patients with acute respiratory failure. Study Design: RARICO is a pragmatic, randomized, controlled, double-blinded, multi-center trial evaluating the safety and feasibility of nebulized revefenacin in comparison to nebulized ipratropium in patients with COPD and acute respiratory failure requiring invasive mechanical ventilation.

Official Title
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Revefenacin in Acute Respiratory Insufficiency in COPD (RARICO)

Conditions
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COPD, Acute Respiratory Failure

Intervention / Treatment
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* Drug: Revefenacin Inhalation Solution [Yupelri]
* Drug: Ipratropium Bromide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults ≥ 40 years of age Acute respiratory failure requiring invasive mechanical ventilation Documented history of COPD based on spirometric evidence of FEV1/FVC<70% Smoking history >10 years (current or prior) Invasive mechanical ventilation for < 96 hours Exclusion Criteria: Chronic invasive mechanical ventilation via tracheostomy. Patients with tracheostomy alone without chronic mechanical ventilation may be enrolled. Expected duration of mechanical ventilation <24 hours Hypersensitivity to muscarinic antagonists Inability to tolerate albuterol Lack of documented COPD history For patients taking short- or long-acting muscarinic antagonists (SAMAs or LAMAs) at the time of screening, inability or unwillingness to undergo the SAMA or LAMA washout period (6 hours or 24 hours, respectively) prior to initiating study drug. Presence of ARDS or acute congestive heart failure Unwillingness or inability to remain on the study drug with for the duration of the study Unwillingness or inability to have open-label muscarinic antagonists withheld for duration of the study Unwillingness or inability to utilize the Puritan-Bennett 980 (PB980) ventilator Pulmonary comorbidities such as pneumothorax or pneumomediastinum that, in the opinion of the investigator or clinical team, can pose a risk to subject safety or interfere with the subject's ability to complete the study procedures. Documented restrictive lung disease or history of interstitial lung disease Actual body weight exceeding 1 kg per centimeter of height Pregnancy AST or ALT > 3 times the upper limit of normal, or other clinically significant acute or chronic liver disease Known history of glaucoma Enrollment in other interventional clinical trial Moribund patient not expected to survive >24 hours Decision to withhold life-sustaining treatment, except in those patients committed to full support except cardiopulmonary resuscitation Inability to obtain informed consent from patient or legally authorized representative (LAR)

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: pragmatic, randomized, controlled, double-blinded
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Revefenacin<br>Revefenacin will be delivered once daily via nebulizer. In order to allow for full blinding and steady Q6 hours regimen in control arm, at hours 6, 12 and 18 after the Revefenacin dose, nebulized normal saline will be delivered. | Drug: Revefenacin Inhalation Solution [Yupelri]<br>* nebulized drug comparison<br>|
| Active Comparator: Ipratropium<br>Nebulized ipratropium will be delivered via nebulizer Q6 hours. | Drug: Ipratropium Bromide<br>* nebulized drug comparison<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in total inspiratory resistance Rstat at the time of drug trough | Reduction in total inspiratory resistance across the airways and ventilator circuit measured by the change in Static Resistance (Rstat) at the time of drug trough | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in total inspiratory resistance Rdyn at the time of drug trough | Reduction in total inspiratory resistance across the airways and ventilator circuit measured by the change in Dynamic Resistance (Rdyn) at the time of drug trough | 7 days | 
| Reduction in Resistive pressure (Pres) at the time of drug trough | Reduction in total inspiratory resistance across the airways and ventilator circuit measured by the change in Resistive pressure (Pres) at the time of drug trough | 7 days | 
| Reduction in total inspiratory resistance Rstat at the time of drug peak | Reduction in total inspiratory resistance across the airways and ventilator circuit measured by the change in Static Resistance (Rstat) at the time of drug peak | 7 days | 
| PaCO2 | Arterial partial pressure of CO2 measured at the drug trough | 7 days | 
| Respiratory therapist time at bedside | RT resource utilization as reflected in the total effective time spent at the bedside providing care | 7 days | 
| ICU Length of stay | Time spent in the ICU from the enrollment in the study through the same-stay discharge from the hospital | Hospital stay, expected to be less than 28 days | 
| Ventilator-free days to day 28 | Time spent ventilator-free from the day of enrollment in the study through the same-stay discharge from the hospital | Hospital stay, expected to be less than 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, Acute Respiratory failure, Long acting muscarinic antagonist, nebulizer, mechanical ventilation