Baricitinib in Symptomatic Patients Infected by COVID-19: an Open-label, Pilot Study.

Study Overview
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Brief Summary
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There is no specific antiviral treatment recommended for COVID-19, and no vaccine is currently available. Baricitinib, an anti-Janus kinase inhibitor (anti-JAK) acting against JAK1 and JAK2. The drug was found capable to reduce or interrupt the passage of the virus into target cells, and to inhibit the JAK1- and JAK2-mediated cytokine release. The drug was licensed for the treatment of rheumatoid arthritis at the daily dose of 4 mg/orally, with excellent results in terms of clinical response and a good safety profile. Since baricitinib does not interact with antivirals due to its prevalent renal elimination, it may be used in combination.The evidence on the advantageous action of baricitinib on viral entry and cytokine outbreak constituted the rationale to perform a trial on patients with mild to moderate COVID-19 infection receiving baricitinib combined with antiviral therapy.

Detailed Description
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Study design. Interventional, open-label, 2-week, prospective trial of a cohort of patients with mild to moderate COVID-19 infection. Objectives. Primary. To assess the efficacy of baricitinib combined with antiviral therapy in patients with COVID-19-related mild and moderate disease in terms of reduction of the percentage of subjects requiring ICU admission. Secondary objectives. To describe the clinical findings in a cohort of symptomatic COVID-19-infected subjects; to investigate the role of CRP, IL-6, and TNFα levels as predictor of progression to ARDS; to assess the type and incidence of adverse events (AEs).

Official Title
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Baricitinib Combined With Antiviral Therapy in Symptomatic Patients Infected by COVID-19: an Open-label, Pilot Study

Conditions
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Pharmacological Action

Intervention / Treatment
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* Drug: Baricitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All consecutive patients with mild to moderate COVID-19 infection Age >18 years, Clinical diagnosis of COVID19 infection Patients should present fever, cough and myalgia and weakness and radiological findings of pneumonia. All patients should be willing and able to provide written informed consent prior to performing study procedures. Exclusion Criteria: Age less than 18 History of thrombophlebitis. Patient with latent tuberculosis infection (Quantiferon test). Pregnancy and lactation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Patients. All consecutive patients with mild to moderate COVID-19 infection, older than 18, Patients should present fever, cough and myalgia and weakness and radiological findings of pneumonia. Controls. All consecutive patients with mild to moderate COVID-19 infection, older than 18, admitted during the previous 2 weeks, who were treated with antiviral and/or hydroxychloroquine.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients<br>All patients received baricitinib combined to antiviral therapy lopinavir/ritonavir for 2 weeks. | Drug: Baricitinib<br>* Baricitinib 4 mg/day/orally combined to antiviral therapy ritonavir for 2 weeks. Baricitinib tablets 4 mg were administered in the morning.<br>* Other names: Lopinavir/Ritonavir tablets 250 mg/bid;|
| Active Comparator: Controls<br>All consecutive patients with mild to moderate COVID-19 infection, older than 18, a during the previous 2 weeks, who were treated with antiviral and/or hydroxychloroquine. | Drug: Baricitinib<br>* Baricitinib 4 mg/day/orally combined to antiviral therapy ritonavir for 2 weeks. Baricitinib tablets 4 mg were administered in the morning.<br>* Other names: Lopinavir/Ritonavir tablets 250 mg/bid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage of patients requiring transfer to ICU as compared with the rate of transfers observed in controls. | The percentage of ICU admission in patients and controls will be compared for statistical difference | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage of patients achieving the remission; CRP, IL-6 and TNFα values at baseline and during the treatment course; the number of AEs. | CRP values will be evaluated for prediction of disease worsening. | 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Baricitinib, Moderate disease, Infection