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Assessment of Efficacy and Safety of Ruxolitinib in Participants With COVID-19-Associated ARDS Who Require Mechanical Ventilation (RUXCOVID-DEVENT)

Phase 3
Terminated
Conditions
COVID-19
Interventions
Drug: Placebo
Registration Number
NCT04377620
Lead Sponsor
Incyte Corporation
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
211
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placebo + Standard of Care (SoC)PlaceboMatching Placebo will be administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.
Ruxolitinib 5mg + Standard of Care (SoC)RuxolitinibRuxolitinib 5mg will be administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.
Ruxolitininb 15mg + Standard of Care (SoC)RuxolitinibRuxolitinib 15mg will be administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants Who Have Died Due to Any CauseStudy start to Day 29

To evaluate the 28-day mortality rate of ruxolitinib 5 mg BID + SoC therapy and ruxolitinib 15 mg BID + SoC compared with placebo + SoC therapy, in participants with COVID-19-associated ARDS who require mechanical ventilation.

Secondary Outcome Measures
NameTimeMethod
Number of Ventilator Free DaysStudy start to Day 29

Number of days participant did not require mechanical ventilation

Oxygen Free DaysStudy start to Day 29

Number of days participant did not receive supplemental oxygen

Vasopressor Free DaysStudy start to Day 29

Number of days without use of vasopressor therapy

Hospital Free DaysStudy start to Day 29

Number of days Partcipant is out of the hospital

Percentage of Participants With at Least 2-point Improvement in the COVID-19 Ordinal ScaleStudy start to Days 15 and 29

Participants with at least 2-point improvement at Day 15 and 29 based on participant state. The scale ranges from 0-8 with 0 being no clinical or virological evidence of infection and 8 being dead

Number of ICU Free DaysStudy start to Day 29

Number of days participant is out of the ICU

Percentage of Participants With the COVID-19 Ordinal Scale ReportedStudy start to Day 29

Clinical status of participant at Day 29 based on participant state. The scale ranges from 0-8 with 0 being no clinical or virological evidence of infection and 8 being dead

Change in SOFA Scorefrom baseline to Days 3, 5, 8, 11, 15, and 29

Sequential Organ Failure Assessment (SOFA) score is a scoring system to determine the extent of a person's organ function or rate of failure. The score is based on 6 different scores, 1 each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems. Each system gets a score from 0 (normal) to 4 (abnormal) and the sum of each score defines the final SOFA score, which 24 is the maximum score (high risk of morality) and 0 is the minimum score (low risk of mortality).

Percentage of Participants With at Least 1-point Improvement in the COVID-19 Ordinal ScaleStudy start to Days 15 and 29

Participants with at lest 1-point improvement in clinical status at Days 15 and 29 based on participant state. The scale ranges from 0-8 with 0 being no clinical or virological evidence of infection and 8 being dead

Number and Percentage of Participants With Treatment-related Side Effects and Serious Adverse EventsStudy start to Day 29

Treatment-emergent AEs are judged as related by the investigator or have a missing causality.

Time to Improvement From Baseline Category to Earliest 1-point Improvement in the COVID-19 Ordinal ScaleStudy Start to Day 29

TIme to improvement compared to baseline. The scale ranges from 0-8 with 0 being no clinical or virological evidence of infection and 8 being dead

Change in the COVID-19 9-point Ordinal ScaleStudy start to Days 15 and 29

Change in the Clinical status of participant at Days 15 and 29 based on participant state. The scale ranges from 0-8 with 0 being no clinical or virological evidence of infection and 8 being dead

Trial Locations

Locations (36)

Temple University

🇺🇸

Philadelphia, Pennsylvania, United States

Wenatchee Valley Hospital and Clinics

🇺🇸

Wenatchee, Washington, United States

Northshore University Health System

🇺🇸

Chicago, Illinois, United States

West Penn Hospital

🇺🇸

Pittsburgh, Pennsylvania, United States

Boston Medical Center

🇺🇸

Boston, Massachusetts, United States

Teradan Clinical Trials

🇺🇸

Brandon, Florida, United States

Honor Health Research Institute

🇺🇸

Scottsdale, Arizona, United States

Sharp Memorial Hospital

🇺🇸

San Diego, California, United States

Indiana University Simon Cancer Center

🇺🇸

Indianapolis, Indiana, United States

Johns Hopkins University

🇺🇸

Baltimore, Maryland, United States

Allegheny Health Network

🇺🇸

Wexford, Pennsylvania, United States

Loyola University Medical Center

🇺🇸

Maywood, Illinois, United States

University of Massachusetts Medical School

🇺🇸

Worcester, Massachusetts, United States

University of Cincinnati

🇺🇸

Cincinnati, Ohio, United States

Duke University Medical Center

🇺🇸

Durham, North Carolina, United States

University of Texas Health Science Center At Houston - McGovern Medical School

🇺🇸

Houston, Texas, United States

East Carolina University

🇺🇸

Greenville, North Carolina, United States

University of Florida

🇺🇸

Gainesville, Florida, United States

Mercy Research

🇺🇸

Springfield, Missouri, United States

Indiana University Health Central Indiana Cancer Centers

🇺🇸

Indianapolis, Indiana, United States

Georgetown University Hospital

🇺🇸

Washington, District of Columbia, United States

Holy Name Medical Center

🇺🇸

Teaneck, New Jersey, United States

Rutgers Njms Clinical Research Unit

🇺🇸

Newark, New Jersey, United States

Lahey Hospital & Medical Center

🇺🇸

Burlington, Massachusetts, United States

Hackensack University Medical Center

🇺🇸

Hackensack, New Jersey, United States

East Jefferson General Hospital

🇺🇸

Metairie, Louisiana, United States

Healthpartners Cancer Care Center - Regions Hospital

🇺🇸

Saint Paul, Minnesota, United States

Jefferson University Hospitals

🇺🇸

Philadelphia, Pennsylvania, United States

University of Rochester Medical Center

🇺🇸

Rochester, New York, United States

Kettering Cancer Care

🇺🇸

Dayton, Ohio, United States

St David'S Medical Center

🇺🇸

Austin, Texas, United States

University of Texas Health Science Cente

🇺🇸

San Antonio, Texas, United States

Sbih City Hospital 15

🇷🇺

Saint Petersburg, Russian Federation

Tampa General Hospital

🇺🇸

Tampa, Florida, United States

University of South Florida

🇺🇸

Tampa, Florida, United States

Aurora Research Institute

🇺🇸

Milwaukee, Wisconsin, United States

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