COVID-19Phase 3NCT04377620

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

A Phase 3 study testing Ruxolitinib in people with COVID-19, run by Incyte Corporation at 36 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

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. Read more about this study

Who is it for?: Ages 12 years and older
Conditions the study is for: COVID-19
What is being tested?: Ruxolitinib
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 211 participants
Where: 36 sitesin 2 countries
Study dates: 24 May 2020to 26 Feb 2021
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 12 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Show all 10Show fewer

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.

Trial locations and contacts

36 sites in 2 countries.

Country

City, postcode or hospital

36 sites in 2 countries

United States35 sites

St David'S Medical Center
Austin, Texas, 78705
Johns Hopkins University
Baltimore, Maryland, 21224
Boston Medical Center
Boston, Massachusetts, 02118
Teradan Clinical Trials
Brandon, Florida, 33511
Lahey Hospital & Medical Center
Burlington, Massachusetts, 01805
Northshore University Health System
Chicago, Illinois, 60678
University of Cincinnati
Cincinnati, Ohio, 45219
Kettering Cancer Care
Dayton, Ohio, 45429
Duke University Medical Center
Durham, North Carolina, 27710
University of Florida
Gainesville, Florida, 32610
East Carolina University
Greenville, North Carolina, 27858
Hackensack University Medical Center
Hackensack, New Jersey, 07601
University of Texas Health Science Center At Houston - McGovern Medical School
Houston, Texas, 77030
Indiana University Simon Cancer Center
Indianapolis, Indiana, 46202
Indiana University Health Central Indiana Cancer Centers
Indianapolis, Indiana, 46219
Loyola University Medical Center
Maywood, Illinois, 60153
East Jefferson General Hospital
Metairie, Louisiana, 70006
Aurora Research Institute
Milwaukee, Wisconsin, 53233
Rutgers Njms Clinical Research Unit
Newark, New Jersey, 07103
Jefferson University Hospitals
Philadelphia, Pennsylvania, 19107
Temple University
Philadelphia, Pennsylvania, 19140
West Penn Hospital
Pittsburgh, Pennsylvania, 15224
University of Rochester Medical Center
Rochester, New York, 14642
Healthpartners Cancer Care Center - Regions Hospital
Saint Paul, Minnesota, 55101
University of Texas Health Science Cente
San Antonio, Texas, 78229
Sharp Memorial Hospital
San Diego, California, 92123
Honor Health Research Institute
Scottsdale, Arizona, 85258
Mercy Research
Springfield, Missouri, 65804
Tampa General Hospital
Tampa, Florida, 33606
University of South Florida
Tampa, Florida, 33613
Holy Name Medical Center
Teaneck, New Jersey, 07666
Georgetown University Hospital
Washington D.C., District of Columbia, 20007
Wenatchee Valley Hospital and Clinics
Wenatchee, Washington, 98801
Allegheny Health Network
Wexford, Pennsylvania, 15090
University of Massachusetts Medical School
Worcester, Massachusetts, 01655

Other trials in United States

Russia1 site

Sbih City Hospital 15
Saint Petersburg, 198205

Other trials in Russia

About this study

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)

Conditions: COVID-19
Being tested: Placebo, Ruxolitinib
Keywords: Cytokine storm, COVID-19, ARDS, SARS-CoV-2, ruxolitinib, pneumonia
Medical subject headings: COVID-19, Cytokine Release Syndrome, Pneumonia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PlaceboDrug
Placebo administered BID approximately 12 hours apart
RuxolitinibDrug
Also called INCB018424, Oral Jak Inhibitor
Ruxolitinb administered BID approximately 12 hours apart

Study groups in NCT04377620
Study group	Role	What they receive
Placebo + Standard of Care (SoC)	Placebo comparator	Matching Placebo will be administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral. Receives: Drug: Placebo
Ruxolitinib 5mg + Standard of Care (SoC)	Experimental	Ruxolitinib 5mg will be administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral. Receives: Drug: Ruxolitinib
Ruxolitininb 15mg + Standard of Care (SoC)	Experimental	Ruxolitinib 15mg will be administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral. Receives: Drug: Ruxolitinib

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Study start to Day 29

Secondary outcomes (12)

Number of Ventilator Free Days
Number of days participant did not require mechanical ventilation
Measured: Study start to Day 29
Number of ICU Free Days
Number of days participant is out of the ICU
Measured: Study start to Day 29
Oxygen Free Days
Number of days participant did not receive supplemental oxygen
Measured: Study start to Day 29
Vasopressor Free Days
Number of days without use of vasopressor therapy
Measured: Study start to Day 29
Hospital Free Days
Number of days Partcipant is out of the hospital
Measured: Study start to Day 29
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
Measured: Study start to Days 15 and 29
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
Measured: Study start to Days 15 and 29
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
Measured: Study Start to Day 29
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
Measured: Study start to Day 29
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
Measured: Study start to Days 15 and 29
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).
Measured: from baseline to Days 3, 5, 8, 11, 15, and 29
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.
Measured: Study start to Day 29

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

24 May 202026 Feb 2021

First posted6 May 2020
Study start24 May 2020
Primary completion26 Feb 2021
Study completion26 Feb 2021

Why it stopped: Study terminated by sponsor

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 (1)Papers the sponsor has linked to this study.
Other trials for COVID-19Studies of the same condition, open and under way.
More trials run by Incyte CorporationThe 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 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 211 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04377620
Sponsor's protocol ID: INCB 18424-369
Status last verified: Jan 2022
First submitted: 4 May 2020
Last updated: 19 Jan 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Undecided
Expanded access: Available

Publications

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.
PubMed 36226977

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 19 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

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)
ClinicalTrials.gov ID: NCT04377620
Acronym / sponsor ID: INCB 18424-369
Conditions: COVID-19
Keywords: Cytokine storm, COVID-19, ARDS, SARS-CoV-2, ruxolitinib, pneumonia
Phase: Phase 3
Study type: Interventional
Recruitment status: TerminatedReason stopped: Study terminated by sponsor
Enrolment: 211 participants (actual)
Lead sponsor: Incyte CorporationIndustry (pharma, biotech, devices)
Study start: 24 May 2020 (actual)
Primary completion: 26 Feb 2021 (actual)
Study completion: 26 Feb 2021 (actual)
First posted: 6 May 2020 (actual)
Results: Posted 19 Jan 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 3

Arm	Type	Receives
Placebo + Standard of Care (SoC)	Placebo comparator	Drug: 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)	Experimental	Drug: 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)	Experimental	Drug: RuxolitinibRuxolitinib 15mg will be administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.

Who may qualify

Ages: 12 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (5 listed)

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.

Key exclusion criteria (10 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PlaceboPlacebo administered BID approximately 12 hours apart	Drug	Placebo + Standard of Care (SoC)
RuxolitinibAlso: INCB018424, Oral Jak InhibitorRuxolitinb administered BID approximately 12 hours apart	Drug	Ruxolitinib 5mg + Standard of Care (SoC), Ruxolitininb 15mg + Standard of Care (SoC)

Primary outcome

Percentage of Participants Who Have Died Due to Any Cause
Time frame: 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.

12 secondary outcomes

Number of Ventilator Free Days
Time frame: Study start to Day 29
Number of ICU Free Days
Time frame: Study start to Day 29
Oxygen Free Days
Time frame: Study start to Day 29
Vasopressor Free Days
Time frame: Study start to Day 29
Hospital Free Days
Time frame: Study start to Day 29
Percentage of Participants With at Least 2-point Improvement in the COVID-19 Ordinal Scale
Time frame: Study start to Days 15 and 29
Percentage of Participants With at Least 1-point Improvement in the COVID-19 Ordinal Scale
Time frame: Study start to Days 15 and 29
Time to Improvement From Baseline Category to Earliest 1-point Improvement in the COVID-19 Ordinal Scale
Time frame: Study Start to Day 29
Percentage of Participants With the COVID-19 Ordinal Scale Reported
Time frame: Study start to Day 29
Change in the COVID-19 9-point Ordinal Scale
Time frame: Study start to Days 15 and 29
Change in SOFA Score
Time frame: from baseline to Days 3, 5, 8, 11, 15, and 29
Number and Percentage of Participants With Treatment-related Side Effects and Serious Adverse Events
Time frame: Study start to Day 29

Results and safety

Results posted to the registry on 19 Jan 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Ruxolitininb 15mg + Standard of Care	77	35
Ruxolitinib 5mg + Standard of Care (SoC)	87	37
Placebo + Standard of Care (SoC)	47	11

Primary outcome: Percentage of Participants Who Have Died Due to Any Cause

Time frame: Study start to Day 29. Number. Unit: Percentage

Measure	Ruxolitininb 15mg + Standard of Care (SoC) n = 77	Ruxolitinib 5mg + Standard of Care (SoC) n = 85	Placebo + Standard of Care (SoC) n = 47
Value	50.6	52.9	70.2

Ruxolitininb 15mg + Standard of Care (SoC): Odds Ratio (OR): 0.46 (95% CI 0.201 to 1.028), p = 0.0292, Mixed Models Analysis
Ruxolitinib 5mg + Standard of Care (SoC): Odds Ratio (OR): 0.42 (95% CI 0.171 to 1.023), p = 0.0280, Mixed Models Analysis

Population analysed: ITT population is defined according to the treatment assignment at the time of randomization regardless of the actual study drug the participant might take during his/her participation in the study.

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to approximately 2 months.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Ruxolitinib 15 mg BID	23 of 77 (29.9%)	35 of 77 (45.5%)	42 of 77
Ruxolitinib 5 mg BID	21 of 87 (24.1%)	46 of 87 (52.9%)	48 of 87
Placebo	11 of 45 (24.4%)	21 of 45 (46.7%)	36 of 47
Total	55 of 209 (26.3%)	102 of 209 (48.8%)	124 of 209

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Jan 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 36226977Rein 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.
Individual participant dataSharing planned: Undecided

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

36 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ruxolitinib in people with COVID-19, run by Incyte Corporation at 36 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 19 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 36 sites in United States, Russia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Jan 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Who Have Died Due to Any Cause (time frame: Study start to Day 29). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04377620, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jan 2022.