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

COVID-19 Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04377620
• Other study ID #: INCB 18424-369
• Status: Terminated
• Phase: Phase 3
• Start date: May 24, 2020
• Est. completion date: February 26, 2021

Study information

• Verified date: January 2022
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 211
• Est. completion date: February 26, 2021
• Est. primary completion date: February 26, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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-1ß, 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.

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• Placebo
Placebo administered BID approximately 12 hours apart
• Ruxolitinib
Ruxolitinb administered BID approximately 12 hours apart

Locations

Country	Name	City	State
Russian Federation	Sbih City Hospital 15	Saint Petersburg
United States	St David'S Medical Center	Austin	Texas
United States	Johns Hopkins University	Baltimore	Maryland
United States	Boston Medical Center	Boston	Massachusetts
United States	Teradan Clinical Trials	Brandon	Florida
United States	Lahey Hospital & Medical Center	Burlington	Massachusetts
United States	Northshore University Health System	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	Kettering Cancer Care	Dayton	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Florida	Gainesville	Florida
United States	East Carolina University	Greenville	North Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	University of Texas Health Science Center At Houston - McGovern Medical School	Houston	Texas
United States	Indiana University Health Central Indiana Cancer Centers	Indianapolis	Indiana
United States	Indiana University Simon Cancer Center	Indianapolis	Indiana
United States	Loyola University Medical Center	Maywood	Illinois
United States	East Jefferson General Hospital	Metairie	Louisiana
United States	Aurora Research Institute	Milwaukee	Wisconsin
United States	Rutgers Njms Clinical Research Unit	Newark	New Jersey
United States	Jefferson University Hospitals	Philadelphia	Pennsylvania
United States	Temple University	Philadelphia	Pennsylvania
United States	West Penn Hospital	Pittsburgh	Pennsylvania
United States	University of Rochester Medical Center	Rochester	New York
United States	Healthpartners Cancer Care Center - Regions Hospital	Saint Paul	Minnesota
United States	University of Texas Health Science Cente	San Antonio	Texas
United States	Sharp Memorial Hospital	San Diego	California
United States	Honor Health Research Institute	Scottsdale	Arizona
United States	Mercy Research	Springfield	Missouri
United States	Tampa General Hospital	Tampa	Florida
United States	University of South Florida	Tampa	Florida
United States	Holy Name Medical Center	Teaneck	New Jersey
United States	Georgetown University Hospital	Washington	District of Columbia
United States	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington
United States	Allegheny Health Network	Wexford	Pennsylvania
United States	University of Massachusetts Medical School	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

United States,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Who Have Died Due to Any Cause	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.	Study start to Day 29
Secondary	Number of Ventilator Free Days	Number of days participant did not require mechanical ventilation	Study start to Day 29
Secondary	Number of ICU Free Days	Number of days participant is out of the ICU	Study start to Day 29
Secondary	Oxygen Free Days	Number of days participant did not receive supplemental oxygen	Study start to Day 29
Secondary	Vasopressor Free Days	Number of days without use of vasopressor therapy	Study start to Day 29
Secondary	Hospital Free Days	Number of days Partcipant is out of the hospital	Study start to Day 29
Secondary	Percentage of Participants With at Least 2-point Improvement in the COVID-19 Ordinal Scale	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	Study start to Days 15 and 29
Secondary	Percentage of Participants With at Least 1-point Improvement in the COVID-19 Ordinal Scale	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	Study start to Days 15 and 29
Secondary	Time to Improvement From Baseline Category to Earliest 1-point Improvement in the COVID-19 Ordinal Scale	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	Study Start to Day 29
Secondary	Percentage of Participants With the COVID-19 Ordinal Scale Reported	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	Study start to Day 29
Secondary	Change in the COVID-19 9-point Ordinal Scale	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	Study start to Days 15 and 29
Secondary	Change in SOFA Score	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).	from baseline to Days 3, 5, 8, 11, 15, and 29
Secondary	Number and Percentage of Participants With Treatment-related Side Effects and Serious Adverse Events	Treatment-emergent AEs are judged as related by the investigator or have a missing causality.	Study start to Day 29