Clinical trial NCT04477993: Ruxolitinib for Acute Respiratory Disorder Syndrome Due to COVID-19
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
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: 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
Lead sponsor: University of Sao Paulo General Hospital
Sponsor class: OTHER
First posted: 2020-07-20
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

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