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

Randomized, Double-Blind Clinical Trial of Ruxolitinib in Patients With Acute Respiratory Disorder Syndrome Due to SARS-CoV-2 Infection

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.

Study Overview

• Status: Terminated
• Conditions: SARS-CoV2; Severe Acute Respiratory Syndrome Coronavirus 2
• Intervention / Treatment: Drug: Janus Kinase Inhibitor (ruxolitinib); Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo, Brazil, 05403-000
    • Hospital das Clínicas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Group	Other: Placebo; Placebo tablets P.O. b.i.d. for 14 days.
Experimental: Experimental Group - ruxolitinib; Ruxolitinib 5 mg PO b.i.d. for 14 days	Drug: Janus Kinase Inhibitor (ruxolitinib); 5 mg P.O. b.i.d. for 14 days. Dose reduction will occur if neutrophils < 500/mm3 or platelets <50,000/mm3.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
A composite outcome of death or ICU admission or mechanical ventilation at day 14.	14 days

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Vanderson Geraldo Rocha

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2020
• Primary Completion (Actual): March 29, 2021
• Study Completion (Actual): March 29, 2021

Study Registration Dates

• First Submitted: July 13, 2020
• First Submitted That Met QC Criteria: July 17, 2020
• First Posted (Actual): July 20, 2020

Study Record Updates

• Last Update Posted (Actual): April 8, 2021
• Last Update Submitted That Met QC Criteria: April 5, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Safety; Clinical Trial; SARS-CoV2; Severe Acute Respiratory Syndrome Coronavirus 2; Janus Kinase Inhibitors; Clinical Efficacy
• Additional Relevant MeSH Terms: Pathologic Processes; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Disease; Severe Acute Respiratory Syndrome; Coronavirus Infections; Syndrome; Respiration Disorders; Respiratory Tract Diseases; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Janus Kinase Inhibitors
• Other Study ID Numbers: 32894720.3.0000.0068

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No