Severe Acute Respiratory Syndrome Coronavirus 2
Conditions
Keywords
Ruxolitinib, Acute Respiratory Distress Syndrome, COVID-19
Brief summary
It is an observational, cohort, retrospective, monocentric, non-profit study. The primary objective is to evaluate the efficacy and safety of ruxolitinib in acute respiratory distress syndrome in patients with SARS-CoV-2 COVID-19 with rapid deterioration of respiratory parameters in the last 12 hours.
Detailed description
It is an observational, cohort, retrospective, monocentric, non-profit study. Patients with SARS-CoV-2 COVID-19 pneumonia who started off-label Ruxolitinib treatment in the period between 25/03/2020 and 07/04/2020 in hospitalization in the COVID-19 wards of the USL Toscana Nord Ovest company. Primary objective \- Evaluation of the efficacy and safety of ruxolitinib in acute respiratory distress syndrome in patients with SARS-CoV-2 COVID-19 with rapid deterioration of respiratory parameters in the last 12 hours. Secondary objectives * Improvement of respiratory performance. * Improvement of acute phase inflammation indices. * Evaluation of known adverse events related to the use of the drug. * Evaluation of the epidemiological parameters in COVID-19 patients. * Monitoring of plasma levels of cytokines before and after treatment. Exploratory objectives * Analysis of the outcomes for the launch of a study on the efficacy and safety of Ruxolitinib in the treatment of ADRS in COVID-19 patients.
Interventions
Ruxolitinib Oral Tablet dosage of at least 20 mg x 2 / day in the first 48 hours
Sponsors
Fondazione C.N.R./Regione Toscana G. Monasterio, Pisa, Italy
Azienda Ospedaliera Universitaria Senese
Azienda Ospedaliero, Universitaria Pisana
Azienda USL Toscana Nord Ovest
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* positive analysis for RT PCR (Shanghai BioTec or Sansure Biotech) for SARS-CoV-2 in a respiratory tract sample; * Imaging (CT / ECO / RX) positive for pneumonia; * Oxygen saturation (SaO2) of 93% or less in the environment; * Partial oxygen pressure ratio (PaO2) on inspired oxygen fraction (FiO2) (PaO2 / FiO2) lower than 250 mg / Hg, but not lower than 100 mg / Hg; * Rapid clinical evolution with worsening of respiratory parameters in the last 12 hours. * Release of informed consent.
Exclusion criteria
* Pregnancy and breastfeeding; * Patients already in assisted breathing with tracheal cannula; * Patients with active and uncompensated serious pathologies previously to the COVID 19 infection; * Known hypersensitivity to ruxolitinib or to any of the excipients listed in section 6.1 of the SPC; * Patients with renal insufficiency; * Patients with positive quantiferon; * Patients with documented uncontrolled bacterial sepsis (excluding procalcitonin increase in the presence of negative blood cultures); * Patients with neutropenia equal to or less than 1000 PMN / mmc; * Patients with thrombocytopenia equal to or less than 100000 / mmc. * HCV and / or HBV positive patients, HIV.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients who avoid mechanical assisted ventilation in acute respiratory distress syndrome in patients with SARS-CoV-2 COVID-19 | 15 days | Number of patients who avoid mechanical assisted ventilation in acute respiratory distress syndrome in patients with SARS-CoV-2 COVID-19 with rapid deterioration of respiratory parameters in the last 12 hours |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of known adverse events related to the use of the drug - fibrinogen | 15 days | every 24 hours fibrinogen value in mg/dl |
| Improvement of respiratory performance - Arterial Blood Gas Analisys - pH | 15 days | ABG (arterial Blood Gas): pH as SI Unit, every 12 hours and in any case in the presence of significant clinical variations. |
| Improvement of respiratory performance - Arterial Blood Gas Analisys - pO2 | 15 days | ABG (arterial Blood Gas): pO2 in mm Hg, every 12 hours and in any case in the presence of significant clinical variations. |
| Improvement of respiratory performance - Arterial Blood Gas Analisys - pCO2 | 15 days | ABG (arterial Blood Gas): pCO2 in mm Hg, every 12 hours and in any case in the presence of significant clinical variations. |
| Improvement of respiratory performance - ratio values | 15 days | PaO2 / FiO2, SatO2 ratio. Vital parameters and respiratory function every 12 hours and in any case in the presence of significant clinical variations. |
| Evaluation of known adverse events related to the use of the drug - transaminases | 15 days | every 24 hours transaminases value in U/L |
| Evaluation of known adverse events related to the use of the drug - aPTT | 15 days | every 24 hours aPTT value in seconds |
| Evaluation of known adverse events related to the use of the drug - INR | 15 days | every 24 hours INR value in % |
| Evaluation of known adverse events related to the use of the drug - D-Dimer | 15 days | every 24 hours D-Dimer value in mgr/ml |
| Evaluation of known adverse events related to the use of the drug - creatinine | 15 days | every 24 hours creatinine serum value in mg/dl |
| Evaluation of known adverse events related to the use of the drug - Leucocytes count | 15 days | Total leucocyte as CBC x10e)/L |
| Evaluation of known adverse events related to the use of the drug - Leucocytes formula | 15 days | formula % on total leucocyte |
| Evaluation of the epidemiological parameters: Chest CT | 15 days | Thoracic imaging, every 48 h: presence, extension and dimension on lung thickening - Chest CT at start and end of treatment, Time elapsed between the onset of clinical symptoms and hospitalization. |
| Evaluation of the epidemiological parameters: Eco Chest | 15 days | Thoracic imaging: every day: presence and number of line B every 48 hours.Time elapsed between the onset of clinical symptoms and hospitalization. |
| Evaluation of the epidemiological parameters: CHEST X-ray | 15 days | Thoracic imaging: presence, extension and dimension on lung thickening - Chest X-ray, Time elapsed between the onset of clinical symptoms and hospitalization. |
| Monitoring of Serum levels of cytokines before and every 48 h from start to to end of treatment | 15 days | Monitoring of serum cytokines (IL-6 in pgr/dL, TNF in pgr/dL) every 48 h |
| Monitoring incidence of treatment Emergent Adverse Events of ruxolitinib therapy | 15 days | Number of AE grade 1 to 4 |
| Evaluation of known adverse events related to the use of the drug - glycemia | 15 days | every 24 hours glycemia value in mg/dl |
Contacts
Primary ContactEnrico Dr Capochiani, hematologist
Backup ContactBarbara Dr Meini, Pharmacist
Outcome results
None listed