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.
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.
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.
Hospital das Clínicas
Sao Paulo, Brazil