Clinical trial NCT04377620: Assessment of Efficacy and Safety of Ruxolitinib in Participants With COVID-19-Associated ARDS Who Require Mechanical Ventilation (RUXCOVID-DEVENT)
Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Assess the Efficacy and Safety of Ruxolitinib in Participants With COVID-19-Associated ARDS Who Require Mechanical Ventilation (RUXCOVID-DEVENT)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: COVID-19
Keywords: Cytokine storm
COVID-19
ARDS
SARS-CoV-2
ruxolitinib
pneumonia
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2020-05-06
Enrollment: 211
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of ruxolitinib in the treatment of participants with COVID-19-associated Acute Respiratory Distress Syndrome (ARDS) who require mechanical ventilation.


Eligibility criteria: Inclusion Criteria:

* Participant or guardian health proxy must provide informed consent before any study assessment is performed.
* Male or female participants aged ≥ 12 years.
* Participants with coronavirus (SARS-CoV-2) infection confirmed ≤ 3 weeks prior to randomization by any test with local regulatory approval.
* Participants who are intubated and receiving mechanical ventilation due to COVID-19-associated ARDS and have a PaO2/FiO2 of ≤ 300 mmHg within 6 -hours of randomization.

Participants with lung imaging showing bilateral or diffuse pulmonary infiltrates on chest x-ray or CT scan.

Exclusion Criteria:

* Known history of hypersensitivity to any drugs or metabolites of similar chemical classes as ruxolitinib.
* Presence of severely impaired renal function defined by estimated creatinine clearance \< 15 mL/min measured or calculated by Cockcroft-Gault equation or calculated by the updated bedside Schwartz equation. Participants must not be receiving CRRT or intermittent hemodialysis at screening.
* In the opinion of the investigator, unlikely to survive for \> 24 hours from randomization.
* Suspected active uncontrolled bacterial, fungal, viral, or other infection (besides COVID-19).
* Currently receiving ECMO.
* Participant may not be sharing a ventilator, or co-ventilating, with any other patient.
* Treatment with anti-IL-6, IL-6R, IL-1RA, IL-1β, or GM-CSF antagonists, or a BTK inhibitor, within 7 days of randomization.
* Treatment with a JAK inhibitor within 30 days of randomization.
* Participants who are on long-term use of antirejection or immunomodulatory drugs.
* Pregnant or nursing (lactating) women.

Primary outcomes:
measure: Percentage of Participants Who Have Died Due to Any Cause
timeFrame: Study start to Day 29
Secondary outcomes:
measure: Number of Ventilator Free Days
timeFrame: Study start to Day 29
measure: Number of ICU Free Days
timeFrame: Study start to Day 29
measure: Oxygen Free Days
timeFrame: Study start to Day 29
measure: Vasopressor Free Days
timeFrame: Study start to Day 29
measure: Hospital Free Days
timeFrame: Study start to Day 29
measure: Percentage of Participants With at Least 2-point Improvement in the COVID-19 Ordinal Scale
timeFrame: Study start to Days 15 and 29
measure: Percentage of Participants With at Least 1-point Improvement in the COVID-19 Ordinal Scale
timeFrame: Study start to Days 15 and 29
measure: Time to Improvement From Baseline Category to Earliest 1-point Improvement in the COVID-19 Ordinal Scale
timeFrame: Study Start to Day 29
measure: Percentage of Participants With the COVID-19 Ordinal Scale Reported
timeFrame: Study start to Day 29
measure: Change in the COVID-19 9-point Ordinal Scale
timeFrame: Study start to Days 15 and 29
measure: Change in SOFA Score
timeFrame: from baseline to Days 3, 5, 8, 11, 15, and 29
measure: Number and Percentage of Participants With Treatment-related Side Effects and Serious Adverse Events
timeFrame: Study start to Day 29
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Honor Health Research Institute
state: Arizona
city: San Diego
country: United States
facility: Sharp Memorial Hospital
state: California
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Brandon
country: United States
facility: Teradan Clinical Trials
state: Florida
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Chicago
country: United States
facility: Northshore University Health System
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Simon Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Health Central Indiana Cancer Centers
state: Indiana
city: Metairie
country: United States
facility: East Jefferson General Hospital
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Hospital & Medical Center
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Medical School
state: Massachusetts
city: Saint Paul
country: United States
facility: Healthpartners Cancer Care Center - Regions Hospital
state: Minnesota
city: Springfield
country: United States
facility: Mercy Research
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Newark
country: United States
facility: Rutgers Njms Clinical Research Unit
state: New Jersey
city: Teaneck
country: United States
facility: Holy Name Medical Center
state: New Jersey
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Dayton
country: United States
facility: Kettering Cancer Care
state: Ohio
city: Philadelphia
country: United States
facility: Jefferson University Hospitals
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: West Penn Hospital
state: Pennsylvania
city: Wexford
country: United States
facility: Allegheny Health Network
state: Pennsylvania
city: Austin
country: United States
facility: St David'S Medical Center
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center At Houston - McGovern Medical School
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Cente
state: Texas
city: Wenatchee
country: United States
facility: Wenatchee Valley Hospital and Clinics
state: Washington
city: Milwaukee
country: United States
facility: Aurora Research Institute
state: Wisconsin
city: Saint Petersburg
country: Russian Federation
facility: Sbih City Hospital 15
Study officials:
References:
citation: Rein L, Calero K, Shah R, Ojielo C, Hudock KM, Lodhi S, Sadaka F, Bellam S, Palma C, Hager DN, Daniel J, Schaub R, O'Hayer K, Theodoropoulos NM. Randomized Phase 3 Trial of Ruxolitinib for COVID-19-Associated Acute Respiratory Distress Syndrome. Crit Care Med. 2022 Dec 1;50(12):1701-1713. doi: 10.1097/CCM.0000000000005682. Epub 2022 Oct 13.