Ruxolitinib in the Treatment of Covid-19

Study Overview
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Brief Summary
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The treatment of COVID-19 severe acute respiratory syndrome with ruxolitinib 5 mg orally every 12 hours during 14 days would stop the disproportionate inflammatory response, causing a reduction in the proportion of patients who show a progression and worsening of the severe acute respiratory syndrome.

Detailed Description
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Primary Objective Evaluate the efficacy of ruxolitinib in the treatment of COVID-19 severe acute respiratory syndrome by means of measuring the proportion of patients with clinical worsening (defined by a requirement of FIO2 50% and/or mechanical respiratory assistance) during 14 days after the commencement of treatment. Secondary Objectives Evaluate the median duration of hospitalization. Median duration after 45 days of commencement of treatment. Evaluate the evolution of systemic inflammation parameters. Evaluation at the beginning (baseline), middle and end of the treatment with ruxolitinib of PCR, LDH, ESD, Ferritin and IL-6. Evaluate COVID-19 mortality rate after 45 days of treatment. Evaluate the proportion of the requirement of mechanical ventilation. Evaluate ruxolitinib adverse reactions with a total follow-up of 45 days. Evaluate the proportion of secondary infections during the treatment with ruxolitinib.

Official Title
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Safety and Efficacy Study of Ruxolitinib in the Treatment of Severe Acute Respiratory Syndrome Due to SARS-COV-2

Conditions
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COVID-19

Intervention / Treatment
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* Drug: INC424 / Ruxolitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥ 18 years. SARS-Cov2 infection confirmed by a validated method. Presence of COVID-19 severe acute respiratory syndrome with: Respiratory rate ≥ 20/min O2 saturation ≤93% with FiO2 of 0.21 Lung images by means of computerized tomography or thorax radiography compatible with respiratory involvement due to COVID-19. Signed informed consent. Exclusion Criteria: Pregnancy or breast-feeding. Platelets < 50,000/mm3. Neutrophils < 1,000/mm3. Hemoglobin < 6 g/dl Creatinine ≥2 mg/dl or creatinine clearance ≤30 ml/min. Total serum bilirubin > 2.0 x upper limit of normal and/or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5 times the upper limit of normal. Known active infection due to HIV, HVC, HVB, Herpes Zoster or Micob Tuberculosis Treatment with Tocilizumab, Baricitinib or Interferon. History of hypersensitivity to ruxolitinib or to any medicine with similar chemical compounds Patients with mechanical respiratory assistance Patients under treatment with Ruxolitinib due to hematological disease Any condition that, according to the Investigator, may interfere with the complete participation of the patient in the study, including the administration of the medicinal product, the limitation of visits, the implication of a risk for the patient or that prevents the correct interpretation of the results. Treatment Suspension Criteria Voluntary decision of the patient Treating physician's decision to discontinue the treatment Drug toxicity grade 3 or higher (CTCAE 5.0). Study Design Experimental, open-label, prospective, single center, add-on (added to the standard treatment) study, compared with the historical control arm. Control arm: It will include patients with COVID-19 Respiratory Syndrome who meet the aforementioned selection criteria and have received the standard of care (SOC). Efforts will be made so that both arms share similar demographic characteristics as regards gender and age group. Ten centers will participate, which will share the same protocol and their results may be jointly analyzed. The expected n per center is 10-15 patients. For the safety assessment as part of the objective, the following parameters will be taken into account: Biochemical changes: (day 1, 8 and 14) Leukocytes, Formula, Hemoglobin, platelets, creatinine, glycemia, PT, Bilirubin, GOT/GPT. Grade 3/4 Toxicity, SAE (Serious Adverse Event) Incidence of discontinuation, suspension or dose-reduction of the study drug. Incidence of secondary infections. Efficacy Assessment: Efficacy will be graded according to the ordinal scale of 8 points. Time to Improvement Time of response consolidation Changes in NEWS table

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Interventional Model Description: Experimental, open-label, prospective, single center, add-on (added to the standard treatment) study, compared with an historical control arm.
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: INC424 / Ruxolitinib|Ruxolitinib 5 mg orally every 12 hours during 14 days. Total Follow-up time will be of 45 days. The reduction of ruxolitinib dose will be considered in cases of drug-related cytopenias. During hospitalization, clinical and laboratory evolution parameters will be recorded daily in the medical history of the patient and in the data collection table of the study. Upon patient's discharge, a follow-up will be conducted until day +45 During hospitalization, adverse events will be monitored daily by means of clinical assessment and laboratory data. After discharge, monitoring of adverse events will continue during the outpatient follow-up. Pro-inflammatory parameters will be assessed at baseline, after one week (day +7) and at the end of treatment (day +14) Ruxolitinib will be associated to the standard of care for COVID-19 of each center. In case of an adverse effect or a need to discontinue the treatment, ruxolitinib should be suspended.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the efficacy of ruxolitinib in the treatment of COVID-19 severe acute respiratory syndrome | Measuring the proportion of patients with clinical worsening (defined by a requirement of FIO2 >50% and/or mechanical respiratory assistance) | during 14 days after the commencement of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the median duration of hospitalization. |  | after 45 days of commencement of treatment. | 
| Evaluate the evolution of systemic inflammation parameters. | Evaluation at the beginning (baseline), middle and end of the treatment with ruxolitinib of PCR, LDH, ESD, Ferritin and IL-6 (if available). | after 45 days of commencement of treatment. | 
| Evaluate COVID-19 mortality rate |  | after 45 days of treatment. | 
| Evaluate the proportion of the requirement of mechanical ventilation. |  | with a total follow-up of 45 days | 
| Evaluate ruxolitinib adverse reactions |  | with a total follow-up of 45 days. | 
| Evaluate the proportion of secondary infections during the treatment with ruxolitinib |  | after 45 days of commencement of treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ruxolitinib, Covid-19, SARS