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; Drug: Ruxolitinib

• 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

Study Timeline

• Study First Submitted: 2020-05-04
• Study First Submitted QC: 2020-05-04
• Study First Posted: 2020-05-06
• Study Start: 2020-05-24
• Primary Completion: 2021-02-26
• Study Completion: 2021-02-26
• Results First Submitted: 2021-11-17
• Status Verified: 2022-01
• Results First Submitted QC: 2022-01-14
• Last Update Submitted: 2022-01-14
• Results First Posted: 2022-01-19
• Last Update Posted: 2022-01-19

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

Group	Intervention	Description
Placebo + Standard of Care (SoC)	Placebo	Matching 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)	Ruxolitinib	Ruxolitinib 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)	Ruxolitinib	Ruxolitinib 15mg will be administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Have Died Due to Any Cause	Study 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

Name	Time	Method
Number of Ventilator Free Days	Study start to Day 29	Number of days participant did not require mechanical ventilation
Oxygen Free Days	Study start to Day 29	Number of days participant did not receive supplemental oxygen
Vasopressor Free Days	Study start to Day 29	Number of days without use of vasopressor therapy
Hospital Free Days	Study 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 Scale	Study 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 Days	Study start to Day 29	Number of days participant is out of the ICU
Percentage of Participants With the COVID-19 Ordinal Scale Reported	Study 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 Score	from 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 Scale	Study 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 Events	Study 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 Scale	Study 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 Scale	Study 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)

Honor Health Research Institute; 🇺🇸 Scottsdale, Arizona, United States

Sharp Memorial Hospital; 🇺🇸 San Diego, California, United States

Georgetown University Hospital; 🇺🇸 Washington, District of Columbia, United States

Teradan Clinical Trials; 🇺🇸 Brandon, Florida, United States

University of Florida; 🇺🇸 Gainesville, Florida, United States

Tampa General Hospital; 🇺🇸 Tampa, Florida, United States

University of South Florida; 🇺🇸 Tampa, Florida, United States

Northshore University Health System; 🇺🇸 Chicago, Illinois, United States

Loyola University Medical Center; 🇺🇸 Maywood, Illinois, United States

Indiana University Simon Cancer Center; 🇺🇸 Indianapolis, Indiana, United States

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