Revefenacin in Acute Respiratory Insufficiency in COPD

COPD Clinical Trial

— RARICO  

Official title:

Revefenacin in Acute Respiratory Insufficiency in COPD (RARICO)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04315558
• Other study ID #: IRB#20-000129
• Status: Recruiting
• Phase: Phase 2
• Start date: November 1, 2020
• Est. completion date: June 30, 2024

Study information

• Verified date: December 2023
• Source: University of California, Los Angeles
• Contact: Leslie Cortes
• Phone: 3102063669
• Email: LeCortez[@]mednet.ucla.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 21
• Est. completion date: June 30, 2024
• Est. primary completion date: June 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Acute Respiratory Failure
• COPD
• Respiratory Insufficiency

Intervention

Drug:
• Revefenacin Inhalation Solution [Yupelri]
nebulized drug comparison
• Ipratropium Bromide
nebulized drug comparison

Locations

Country	Name	City	State
United States	Ronald Reagan Medical Center at UCLA	Los Angeles	California
United States	Santa Monica UCLA	Santa Monica	California

Sponsors (3)

Lead Sponsor	Collaborator
University of California, Los Angeles	Mylan Pharmaceuticals Inc, Theravance Biopharma

Country where clinical trial is conducted

United States, 

References & Publications (12)

Acute Respiratory Distress Syndrome Network; Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000 May 4;342(18):1301-8. doi: 10.1056/NEJM200005043421801. — View Citation

Breen D, Churches T, Hawker F, Torzillo PJ. Acute respiratory failure secondary to chronic obstructive pulmonary disease treated in the intensive care unit: a long term follow up study. Thorax. 2002 Jan;57(1):29-33. doi: 10.1136/thorax.57.1.29. — View Citation

Donohue JF, Feldman G, Sethi S, Barnes CN, Pendyala S, Bourdet D, Crater G. Cardiovascular safety of revefenacin, a once-daily, lung-selective, long-acting muscarinic antagonist for nebulized therapy of chronic obstructive pulmonary disease: Evaluation in phase 3 clinical trials. Pulm Pharmacol Ther. 2019 Aug;57:101808. doi: 10.1016/j.pupt.2019.101808. Epub 2019 May 30. — View Citation

Donohue JF, Kerwin E, Sethi S, Haumann B, Pendyala S, Dean L, Barnes CN, Moran EJ, Crater G. Revefenacin, a once-daily, lung-selective, long-acting muscarinic antagonist for nebulized therapy: Safety and tolerability results of a 52-week phase 3 trial in moderate to very severe chronic obstructive pulmonary disease. Respir Med. 2019 Jul;153:38-43. doi: 10.1016/j.rmed.2019.05.010. Epub 2019 May 23. — View Citation

Ferguson GT, Feldman G, Pudi KK, Barnes CN, Moran EJ, Haumann B, Pendyala S, Crater G. Improvements in Lung Function with Nebulized Revefenacin in the Treatment of Patients with Moderate to Very Severe COPD: Results from Two Replicate Phase III Clinical Trials. Chronic Obstr Pulm Dis. 2019 Apr 9;6(2):154-165. doi: 10.15326/jcopdf.6.2.2018.0152. Epub 2019 Apr 9. — View Citation

Khan SY, O'Driscoll BR. Is nebulized saline a placebo in COPD? BMC Pulm Med. 2004 Sep 30;4:9. doi: 10.1186/1471-2466-4-9. — View Citation

Maqsood MH, Rubab K, Maqsood MA. The Role of Revefenacin in Chronic Obstructive Pulmonary Disease. Cureus. 2019 Apr 10;11(4):e4428. doi: 10.7759/cureus.4428. — View Citation

Ogale SS, Lee TA, Au DH, Boudreau DM, Sullivan SD. Cardiovascular events associated with ipratropium bromide in COPD. Chest. 2010 Jan;137(1):13-9. doi: 10.1378/chest.08-2367. Epub 2009 Apr 10. — View Citation

Quinn D, Barnes CN, Yates W, Bourdet DL, Moran EJ, Potgieter P, Nicholls A, Haumann B, Singh D. Pharmacodynamics, pharmacokinetics and safety of revefenacin (TD-4208), a long-acting muscarinic antagonist, in patients with chronic obstructive pulmonary disease (COPD): Results of two randomized, double-blind, phase 2 studies. Pulm Pharmacol Ther. 2018 Feb;48:71-79. doi: 10.1016/j.pupt.2017.10.003. Epub 2017 Oct 4. — View Citation

Rezaie N, Shams-Hosseini NS, Kashanizadeh A, Karimi MA. Ipratropium bromide is more effective than Salmeterol - Fluticason combination on O2 saturation patients with COPD. J Res Med Sci. 2013 Aug;18(8):731. No abstract available. — View Citation

Sessler CN, Gosnell MS, Grap MJ, Brophy GM, O'Neal PV, Keane KA, Tesoro EP, Elswick RK. The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med. 2002 Nov 15;166(10):1338-44. doi: 10.1164/rccm.2107138. — View Citation

Zielinski J. Effects of ipratropium bromide on pulmonary hemodynamics in COPD. Chest. 1995 Oct;108(4):1181-2. doi: 10.1378/chest.108.4.1181-b. No abstract available. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory: Ventilator compliance analysis (ventilator dyssynchrony, pressure-volume curve analysis, expiratory flow curve analysis)	Ventilator compliance analysis (ventilator dyssynchrony, pressure-volume curve analysis, expiratory flow curve analysis)	7 days
Other	Safety: Paradoxical bronchospasm, Hypersensitivity reaction, Severe urinary retention not explained by other reasons, Severe constipation not explained by other reasons	Number of episodes of paradoxical bronchospasm, Hypersensitivity reaction, Severe urinary retention not explained by other reasons, Severe constipation not explained by other reasons	7 days
Primary	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	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
Secondary	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
Secondary	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
Secondary	PaCO2	Arterial partial pressure of CO2 measured at the drug trough	7 days
Secondary	Respiratory therapist time at bedside	RT resource utilization as reflected in the total effective time spent at the bedside providing care	7 days
Secondary	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
Secondary	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