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Revefenacin in Acute Respiratory Insufficiency in COPD (RARICO)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04315558
Recruitment Status : Recruiting
First Posted : March 19, 2020
Last Update Posted : September 7, 2022
Sponsor:
Collaborators:
Theravance Biopharma
Mylan Pharmaceuticals Inc
Information provided by (Responsible Party):
Igor Barjaktarevic, MD, PhD, University of California, Los Angeles

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.

Condition or disease Intervention/treatment Phase
COPD Acute Respiratory Failure Drug: Revefenacin Inhalation Solution [Yupelri] Drug: Ipratropium Bromide Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 21 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: pragmatic, randomized, controlled, double-blinded
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: blinded medication delivery
Primary Purpose: Treatment
Official Title: Revefenacin in Acute Respiratory Insufficiency in COPD (RARICO)
Actual Study Start Date : November 1, 2020
Estimated Primary Completion Date : June 1, 2023
Estimated Study Completion Date : June 30, 2023


Arm Intervention/treatment
Experimental: Revefenacin
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]
nebulized drug comparison

Active Comparator: Ipratropium
Nebulized ipratropium will be delivered via nebulizer Q6 hours.
Drug: Ipratropium Bromide
nebulized drug comparison




Primary Outcome Measures :
  1. Reduction in total inspiratory resistance Rstat at the time of drug trough [ Time Frame: 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 Outcome Measures :
  1. Reduction in total inspiratory resistance Rdyn at the time of drug trough [ Time Frame: 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

  2. Reduction in Resistive pressure (Pres) at the time of drug trough [ Time Frame: 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

  3. Reduction in total inspiratory resistance Rstat at the time of drug peak [ Time Frame: 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

  4. PaCO2 [ Time Frame: 7 days ]
    Arterial partial pressure of CO2 measured at the drug trough

  5. Respiratory therapist time at bedside [ Time Frame: 7 days ]
    RT resource utilization as reflected in the total effective time spent at the bedside providing care

  6. ICU Length of stay [ Time Frame: 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

  7. Ventilator-free days to day 28 [ Time Frame: 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


Other Outcome Measures:
  1. Exploratory: Ventilator compliance analysis (ventilator dyssynchrony, pressure-volume curve analysis, expiratory flow curve analysis) [ Time Frame: 7 days ]
    Ventilator compliance analysis (ventilator dyssynchrony, pressure-volume curve analysis, expiratory flow curve analysis)

  2. Safety: Paradoxical bronchospasm, Hypersensitivity reaction, Severe urinary retention not explained by other reasons, Severe constipation not explained by other reasons [ Time Frame: 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



Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04315558


Contacts
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Contact: Leslie Cortes 3102063669 LeCortez@mednet.ucla.edu
Contact: Maria (Carmela) Granone, MD 3108255316 MGranone@mednet.ucla.edu

Locations
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United States, California
Ronald Reagan Medical Center at UCLA Recruiting
Los Angeles, California, United States, 90095
Contact: Marissa Dembek    310-825-2616    mdembek@mednet.ucla.edu   
Contact: Nida Qadir, MD    3108258599    nqadir@mednet.ucla.edu   
Principal Investigator: Nida Qadir, MD         
Santa Monica UCLA Not yet recruiting
Santa Monica, California, United States, 90404
Contact: Marissa Dembek    310-825-2616    mdembek@mednet.ucla.edu   
Contact: Joanne Bando, MD    3104490939    jbando@mednet.ucla.edu   
Principal Investigator: Joanne Bando, MD         
Sponsors and Collaborators
University of California, Los Angeles
Theravance Biopharma
Mylan Pharmaceuticals Inc
Investigators
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Principal Investigator: Igor Z Barjaktarevic, MD, PhD University of California, Los Angeles
Study Director: Donald Tashkin, MD University of California, Los Angeles
Publications:

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Responsible Party: Igor Barjaktarevic, MD, PhD, Principal Investigator, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT04315558    
Other Study ID Numbers: IRB#20-000129
First Posted: March 19, 2020    Key Record Dates
Last Update Posted: September 7, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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.: No
Keywords provided by Igor Barjaktarevic, MD, PhD, University of California, Los Angeles:
COPD
Acute Respiratory failure
Long acting muscarinic antagonist
nebulizer
mechanical ventilation
Additional relevant MeSH terms:
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Respiratory Insufficiency
Respiration Disorders
Respiratory Tract Diseases
Bromides
Ipratropium
Anticonvulsants
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action