Ruxolitinib for Acute Respiratory Disorder Syndrome Due to COVID-19

SARS-CoV2 Clinical Trial

— RUXO-COVID  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04477993
• Other study ID #: 32894720.3.0000.0068
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: August 14, 2020
• Est. completion date: March 29, 2021

Study information

• Verified date: April 2021
• Source: University of Sao Paulo General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: March 29, 2021
• Est. primary completion date: March 29, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 95 Years

Eligibility

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.

Related Conditions & MeSH terms

• Coronavirus Infections
• Respiration Disorders
• Respiratory Tract Diseases
• SARS-CoV2
• Severe Acute Respiratory Syndrome
• Severe Acute Respiratory Syndrome Coronavirus 2
• Syndrome

Intervention

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.

Other:
• Placebo
Placebo tablets P.O. b.i.d. for 14 days.

Locations

Country	Name	City	State
Brazil	Hospital das Clínicas	Sao Paulo

Sponsors (1)

Lead Sponsor	Collaborator
Vanderson Geraldo Rocha

Country where clinical trial is conducted

Brazil, 

Outcome

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