search
Back to results

Ruxolitinib for Acute Respiratory Disorder Syndrome Due to COVID-19 (RUXO-COVID)

Primary Purpose

Severe Acute Respiratory Syndrome Coronavirus 2, SARS-CoV2

Status
Terminated
Phase
Phase 2
Locations
Brazil
Study Type
Interventional
Intervention
Janus Kinase Inhibitor (ruxolitinib)
Placebo
Sponsored by
Vanderson Geraldo Rocha
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Severe Acute Respiratory Syndrome Coronavirus 2 focused on measuring SARS-CoV2, Severe Acute Respiratory Syndrome Coronavirus 2, Janus Kinase Inhibitors, Safety, Clinical Efficacy, Clinical Trial

Eligibility Criteria

18 Years - 95 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients hospitalized with SARS-CoV-2 pneumonia confirmed by RT-PCR or serology (IgA);
  • PaO2/FiO2 < 300 (not fully explained by heart failure or volume overload) or SpO2 < 90% on room air.

Exclusion Criteria:

  • Symptom onset > 14 days;
  • Neutrophil count < 1,000/mm3;
  • Platelets < 50,000/mm3;
  • ICU care at enrollment;
  • On invasive mechanical ventilation at enrollment;
  • Current use of experimental therapy for COVID-19 (except: azithromycin or corticosteroids)
  • Uncontrolled arterial hypertension;
  • Current or previous use of systemic immunosuppressive therapy in the last 30 days;
  • Pregnancy or lactation;
  • Estimated creatinine clearance < 30 mL/min or receiving CRRT or intermittent hemodialysis;
  • Allergy to ruxolitinib;
  • Active tuberculosis;
  • HIV seropositivity;
  • Prior history of progressive multifocal leukoencephalopathy;
  • Use of any JAK inhibitor in the last 30 days before study enrollment;
  • Not qualifying according to investigators' perception.

Sites / Locations

  • Hospital das Clínicas

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Experimental Group - ruxolitinib

Placebo Group

Arm Description

Ruxolitinib 5 mg PO b.i.d. for 14 days

Outcomes

Primary Outcome Measures

A composite outcome of death or ICU admission or mechanical ventilation at day 14.

Secondary Outcome Measures

A composite outcome of death or ICU admission or mechanical ventilation at day 28
Time to treatment failure
ICU admission, mechanical ventilation, death or consent withdrawal
Overall survival at days 14 and 28
Cumulative incidence of ICU admission rate at days 14 and 28
Cumulative incidence of mechanical ventilation at days 14 and 28
Duration of hospital stay
Duration of ICU stay
Duration of mechanical ventilation
Duration of non-invasive ventilation
Secondary hemophagocytic syndrome rate
Cumulative incidence nosocomial infection rate at days 14 and 28
Incidence of discontinuation of oxygen supplementation at days 14 and 28
Rate of grade 1-2 and 3-5 emerging adverse events at day 28
Cumulative dose of methylprednisolone at days 14 and 28
Change in PaO2/FiO2 ratio from baseline to days 14 and 28
Change in interleukin 6 levels [pg/mL] from baseline to days 14 and 28
Change in d-dimer levels [ng/mL] from baseline to days 14 and 28
Change in fibrinogen levels [mg/dL] from baseline to days 14 and 28
Change in ferritin levels [ng/mL] from baseline to days 14 and 28
Change in C reactive protein levels [mg/L] from baseline to days 14 and 28
Change in alanine aminotransferase [U/L] from baseline to days 14 and 28
Change in aspartate aminotransferase [U/L] from baseline to days 14 and 28
Change in creatinine levels [mg/dL] from baseline to days 14 and 28
Change in glucose levels [mg/dL] from baseline to days 14 and 28
Change in hemoglobin levels [g/dL] from baseline to days 14 and 28
Change in platelet count [x10ˆ3/mmˆ3] from baseline to days 14 and 28
Change in absolute neutrophil count [x10ˆ3/mmˆ3] from baseline to days 14 and 28
Change in absolute neutrophil count [/mmˆ3] from baseline to days 14 and 28
Change in absolute lymphocyte count [/mmˆ3] from baseline to days 14 and 28
Change in prothrombin time ratio from baseline to days 14 and 28
Change in partial thromboplastin time ratio from baseline to days 14 and 28
Change in bilirubin [mg/dl] from baseline to days 14 and 28
Change in lactate dehydrogenase [U/L] from baseline to days 14 and 28
Change in CPK-MB [ng/mL] from baseline to days 14 and 28
Change in troponin [ng/mL] from baseline to days 14 and 28
Change in von Willebrand factor antigen level (VWF:Ag) [%] from baseline to days 14 and 28
Change in von Willebrand factor activity (ristocetin cofactor) [%] from baseline to days 14 and 28
Change in ADAMTS-13 [%] from baseline to days 14 and 28
Change in von Willebrand multimeters from baseline to days 14 and 28
Change in plasminogen activator inhibitor-1 levels [ng/mL] from baseline to days 14 and 28
Change in E-selectin levels [ng/mL] from baseline to days 14 and 28
Change in P-selectin levels [ng/mL] from baseline to days 14 and 28
Change in endothelin [fmol/mL] from baseline to days 14 and 28
Change in circulating microparticles from baseline to days 14 and 28
Change in thromboelastography from baseline to days 14 and 28

Full Information

First Posted
July 13, 2020
Last Updated
April 5, 2021
Sponsor
Vanderson Geraldo Rocha
search

1. Study Identification

Unique Protocol Identification Number
NCT04477993
Brief Title
Ruxolitinib for Acute Respiratory Disorder Syndrome Due to COVID-19
Acronym
RUXO-COVID
Official Title
Randomized, Double-Blind Clinical Trial of Ruxolitinib in Patients With Acute Respiratory Disorder Syndrome Due to SARS-CoV-2 Infection
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Terminated
Why Stopped
Low accrual
Study Start Date
August 14, 2020 (Actual)
Primary Completion Date
March 29, 2021 (Actual)
Study Completion Date
March 29, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Vanderson Geraldo Rocha

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The COVID-19 pandemic has had a dramatic effect in public health worldwide. In Brazil, there have been more than 2 million confirmed cases and over 75,000 deaths since February 26, 2020. Based on reports of a hyperinflammatory state associated with COVID-19, the use of immunosuppressive drugs may be efficacious in the treatment of this disease. JAK inhibitors have been shown to harness inflammation in a number of different pathologic conditions. The aim of the present study is to evaluate the efficacy and safety of JAK inhibitor ruxolitinib in patients with acute respiratory distress syndrome due to COVID-19.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Acute Respiratory Syndrome Coronavirus 2, SARS-CoV2
Keywords
SARS-CoV2, Severe Acute Respiratory Syndrome Coronavirus 2, Janus Kinase Inhibitors, Safety, Clinical Efficacy, Clinical Trial

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
5 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Experimental Group - ruxolitinib
Arm Type
Experimental
Arm Description
Ruxolitinib 5 mg PO b.i.d. for 14 days
Arm Title
Placebo Group
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Janus Kinase Inhibitor (ruxolitinib)
Intervention Description
5 mg P.O. b.i.d. for 14 days. Dose reduction will occur if neutrophils < 500/mm3 or platelets <50,000/mm3.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo tablets P.O. b.i.d. for 14 days.
Primary Outcome Measure Information:
Title
A composite outcome of death or ICU admission or mechanical ventilation at day 14.
Time Frame
14 days
Secondary Outcome Measure Information:
Title
A composite outcome of death or ICU admission or mechanical ventilation at day 28
Time Frame
28 days
Title
Time to treatment failure
Description
ICU admission, mechanical ventilation, death or consent withdrawal
Time Frame
28 days
Title
Overall survival at days 14 and 28
Time Frame
14 and 28 days
Title
Cumulative incidence of ICU admission rate at days 14 and 28
Time Frame
14 and 28 days
Title
Cumulative incidence of mechanical ventilation at days 14 and 28
Time Frame
14 and 28 days
Title
Duration of hospital stay
Time Frame
28 days
Title
Duration of ICU stay
Time Frame
28 days
Title
Duration of mechanical ventilation
Time Frame
28 days
Title
Duration of non-invasive ventilation
Time Frame
28 days
Title
Secondary hemophagocytic syndrome rate
Time Frame
28 days
Title
Cumulative incidence nosocomial infection rate at days 14 and 28
Time Frame
14 and 28 days
Title
Incidence of discontinuation of oxygen supplementation at days 14 and 28
Time Frame
14 and 28 days
Title
Rate of grade 1-2 and 3-5 emerging adverse events at day 28
Time Frame
28 days
Title
Cumulative dose of methylprednisolone at days 14 and 28
Time Frame
14 and 28 days
Title
Change in PaO2/FiO2 ratio from baseline to days 14 and 28
Time Frame
14 and 28 days
Title
Change in interleukin 6 levels [pg/mL] from baseline to days 14 and 28
Time Frame
14 and 28 days
Title
Change in d-dimer levels [ng/mL] from baseline to days 14 and 28
Time Frame
14 and 28 days
Title
Change in fibrinogen levels [mg/dL] from baseline to days 14 and 28
Time Frame
14 and 28 days
Title
Change in ferritin levels [ng/mL] from baseline to days 14 and 28
Time Frame
14 and 28 days
Title
Change in C reactive protein levels [mg/L] from baseline to days 14 and 28
Time Frame
14 and 28 days
Title
Change in alanine aminotransferase [U/L] from baseline to days 14 and 28
Time Frame
14 and 28 days
Title
Change in aspartate aminotransferase [U/L] from baseline to days 14 and 28
Time Frame
14 and 28 days
Title
Change in creatinine levels [mg/dL] from baseline to days 14 and 28
Time Frame
14 and 28 days
Title
Change in glucose levels [mg/dL] from baseline to days 14 and 28
Time Frame
14 and 28 days
Title
Change in hemoglobin levels [g/dL] from baseline to days 14 and 28
Time Frame
14 and 28 days
Title
Change in platelet count [x10ˆ3/mmˆ3] from baseline to days 14 and 28
Time Frame
14 and 28 days
Title
Change in absolute neutrophil count [x10ˆ3/mmˆ3] from baseline to days 14 and 28
Time Frame
14 and 28 days
Title
Change in absolute neutrophil count [/mmˆ3] from baseline to days 14 and 28
Time Frame
14 and 28 days
Title
Change in absolute lymphocyte count [/mmˆ3] from baseline to days 14 and 28
Time Frame
14 and 28 days
Title
Change in prothrombin time ratio from baseline to days 14 and 28
Time Frame
14 and 28 days
Title
Change in partial thromboplastin time ratio from baseline to days 14 and 28
Time Frame
14 and 28 days
Title
Change in bilirubin [mg/dl] from baseline to days 14 and 28
Time Frame
14 and 28 days
Title
Change in lactate dehydrogenase [U/L] from baseline to days 14 and 28
Time Frame
14 and 28 days
Title
Change in CPK-MB [ng/mL] from baseline to days 14 and 28
Time Frame
14 and 28 days
Title
Change in troponin [ng/mL] from baseline to days 14 and 28
Time Frame
14 and 28 days
Title
Change in von Willebrand factor antigen level (VWF:Ag) [%] from baseline to days 14 and 28
Time Frame
14 and 28 days
Title
Change in von Willebrand factor activity (ristocetin cofactor) [%] from baseline to days 14 and 28
Time Frame
14 and 28 days
Title
Change in ADAMTS-13 [%] from baseline to days 14 and 28
Time Frame
14 and 28 days
Title
Change in von Willebrand multimeters from baseline to days 14 and 28
Time Frame
14 and 28 days
Title
Change in plasminogen activator inhibitor-1 levels [ng/mL] from baseline to days 14 and 28
Time Frame
14 and 28 days
Title
Change in E-selectin levels [ng/mL] from baseline to days 14 and 28
Time Frame
14 and 28 days
Title
Change in P-selectin levels [ng/mL] from baseline to days 14 and 28
Time Frame
14 and 28 days
Title
Change in endothelin [fmol/mL] from baseline to days 14 and 28
Time Frame
14 and 28 days
Title
Change in circulating microparticles from baseline to days 14 and 28
Time Frame
14 and 28 days
Title
Change in thromboelastography from baseline to days 14 and 28
Time Frame
14 and 28 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
95 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients hospitalized with SARS-CoV-2 pneumonia confirmed by RT-PCR or serology (IgA); PaO2/FiO2 < 300 (not fully explained by heart failure or volume overload) or SpO2 < 90% on room air. Exclusion Criteria: Symptom onset > 14 days; Neutrophil count < 1,000/mm3; Platelets < 50,000/mm3; ICU care at enrollment; On invasive mechanical ventilation at enrollment; Current use of experimental therapy for COVID-19 (except: azithromycin or corticosteroids) Uncontrolled arterial hypertension; Current or previous use of systemic immunosuppressive therapy in the last 30 days; Pregnancy or lactation; Estimated creatinine clearance < 30 mL/min or receiving CRRT or intermittent hemodialysis; Allergy to ruxolitinib; Active tuberculosis; HIV seropositivity; Prior history of progressive multifocal leukoencephalopathy; Use of any JAK inhibitor in the last 30 days before study enrollment; Not qualifying according to investigators' perception.
Facility Information:
Facility Name
Hospital das Clínicas
City
Sao Paulo
ZIP/Postal Code
05403-000
Country
Brazil

12. IPD Sharing Statement

Learn more about this trial

Ruxolitinib for Acute Respiratory Disorder Syndrome Due to COVID-19

We'll reach out to this number within 24 hrs