Acute Respiratory Failure, COPD
Conditions
Keywords
COPD, Acute Respiratory failure, Long acting muscarinic antagonist, nebulizer, mechanical ventilation
Brief summary
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
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.
Interventions
DRUGRevefenacin Inhalation Solution [Yupelri]
nebulized drug comparison
DRUGIpratropium Bromide
nebulized drug comparison
Sponsors
Theravance Biopharma
Mylan Pharmaceuticals Inc
University of California, Los Angeles
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
blinded medication delivery
Intervention model description
pragmatic, randomized, controlled, double-blinded
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reduction in total inspiratory resistance Rstat at the time of drug trough | 7 days | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Reduction in total inspiratory resistance Rdyn at the time of drug trough | 7 days | 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 |
| Reduction in Resistive pressure (Pres) at the time of drug trough | 7 days | 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 |
| Reduction in total inspiratory resistance Rstat at the time of drug peak | 7 days | 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 |
| PaCO2 | 7 days | Arterial partial pressure of CO2 measured at the drug trough |
| ICU Length of stay | Hospital stay, expected to be less than 28 days | Time spent in the ICU from the enrollment in the study through the same-stay discharge from the hospital |
| Ventilator-free days to day 28 | Hospital stay, expected to be less than 28 days | Time spent ventilator-free from the day of enrollment in the study through the same-stay discharge from the hospital |
| Respiratory therapist time at bedside | 7 days | RT resource utilization as reflected in the total effective time spent at the bedside providing care |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory: Ventilator compliance analysis (ventilator dyssynchrony, pressure-volume curve analysis, expiratory flow curve analysis) | 7 days | Ventilator compliance analysis (ventilator dyssynchrony, pressure-volume curve analysis, expiratory flow curve analysis) |
| Safety: Paradoxical bronchospasm, Hypersensitivity reaction, Severe urinary retention not explained by other reasons, Severe constipation not explained by other reasons | 7 days | Number of episodes of paradoxical bronchospasm, Hypersensitivity reaction, Severe urinary retention not explained by other reasons, Severe constipation not explained by other reasons |
Countries
United States
Outcome results
None listed