COPDPhase 2RARICONCT04315558
Revefenacin in Acute Respiratory Insufficiency in COPD
A Phase 2 study testing Revefenacin Inhalation Solution [Yupelri] and Ipratropium Bromide in people with COPD and Acute Respiratory Failure, run by University of California, Los Angeles at 2 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- COPD, Acute Respiratory Failure
- What is being tested?
- Revefenacin Inhalation Solution [Yupelri] and Ipratropium Bromide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Nov 2020to 1 Jan 2025
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 20Show fewer
- 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)
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Ronald Reagan Medical Center at UCLA
Los Angeles, California, 90095
Santa Monica UCLA
Santa Monica, California, 90404
About this study
Official title: Revefenacin in Acute Respiratory Insufficiency in COPD (RARICO)
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.
Read the 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.
- Conditions
- COPD, Acute Respiratory Failure
- Being tested
- Revefenacin Inhalation Solution [Yupelri], Ipratropium Bromide
- Keywords
- COPD, Acute Respiratory failure, Long acting muscarinic antagonist, nebulizer, mechanical ventilation
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Revefenacin Inhalation Solution [Yupelri]Drug
nebulized drug comparison
Ipratropium BromideDrug
nebulized drug comparison
| Study group | Role | What they receive |
|---|---|---|
| Revefenacin | Experimental | 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. Receives: Drug: Revefenacin Inhalation Solution [Yupelri] |
| Ipratropium | Active comparator | Nebulized ipratropium will be delivered via nebulizer Q6 hours. Receives: Drug: Ipratropium Bromide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Respiratory Therapist Time Spent at the Bedside (Minutes Per Day)
Respiratory therapist time spent delivering either Revefenacin or Ipratropium at the bedside (minutes per day)
Measured: 7 days
Secondary outcomes (3)
Safety of Revefenacin: Paradoxical Bronchospasm, Hypersensitivity Reaction, Severe Urinary Retention Not Explained by Other Reasons, Severe Constipation Not Explained by Other Reasons
Number of participants who experienced adverse events not explained by other reasons
Measured: 7 days
Reduction in Total Inspiratory Resistance Rdyn at the Time of Drug Trough
Measured: From the peak to trough within 24 hours
Ventilator Days to Day 28
Time spent on ventilator from the day of enrollment in the study through Day 28
Measured: 28 days post enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2020
- Study start1 Nov 2020
- Primary completion1 Jan 2025
- Study completion1 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for COPDStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- pragmatic, randomized, controlled, double-blinded
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Collaborators
- Theravance Biopharma, Mylan Pharmaceuticals Inc
- Responsible party
- Principal investigator, Igor Barjaktarevic, MD, PhD, University of California, Los Angeles
- Investigators
- Igor Z Barjaktarevic, MD, PhD, Principal investigator, University of California, Los AngelesDonald Tashkin, MD, Study director, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04315558
- Sponsor's protocol ID
- IRB#20-000129
- Acronym
- RARICO
- Status last verified
- Sep 2026
- First submitted
- 16 Mar 2020
- Last updated
- 14 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 31150963Ferguson 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.
PubMed 30974049Donohue 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.
PubMed 31152911Quinn 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.
PubMed 28987804Zielinski 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.
PubMed 7555146Rezaie 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.
PubMed 24379853Ogale 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.
PubMed 19363211Khan 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.
PubMed 15458566Sessler 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.
PubMed 12421743Breen 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.
PubMed 11809986Acute 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.
PubMed 10793162Maqsood 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.
PubMed 31245215