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Ruxolitinib for the Treatment of Acute Respiratory Distress Syndrome in Patients With COVID-19 Infection

Conditions
Severe Acute Respiratory Syndrome Coronavirus 2
Interventions
Registration Number
NCT04361903
Lead Sponsor
Azienda USL Toscana Nord Ovest
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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
13
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.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Patients treated with ruxolutinibRuxolitinib Oral TabletSARS-CoV-2 COVID-19 patients with rapid worsening of respiratory parameters in the last 12 hours treated with ruxolutinib, dosage of at least 20 mg x 2 / day in the first 48 hours.
Primary Outcome Measures
NameTimeMethod
Number of patients who avoid mechanical assisted ventilation in acute respiratory distress syndrome in patients with SARS-CoV-2 COVID-1915 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 Outcome Measures
NameTimeMethod
Improvement of respiratory performance - Arterial Blood Gas Analisys - pCO215 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 values15 days

PaO2 / FiO2, SatO2 ratio. Vital parameters and respiratory function every 12 hours and in any case in the presence of significant clinical variations.

Improvement of respiratory performance - Arterial Blood Gas Analisys - pH15 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 - pO215 days

ABG (arterial Blood Gas): pO2 in mm Hg, 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 - D-Dimer15 days

every 24 hours D-Dimer value in mgr/ml

Evaluation of known adverse events related to the use of the drug - fibrinogen15 days

every 24 hours fibrinogen value in mg/dl

Evaluation of known adverse events related to the use of the drug - transaminases15 days

every 24 hours transaminases value in U/L

Evaluation of known adverse events related to the use of the drug - aPTT15 days

every 24 hours aPTT value in seconds

Evaluation of known adverse events related to the use of the drug - INR15 days

every 24 hours INR value in %

Evaluation of known adverse events related to the use of the drug - glycemia15 days

every 24 hours glycemia value in mg/dl

Evaluation of known adverse events related to the use of the drug - creatinine15 days

every 24 hours creatinine serum value in mg/dl

Evaluation of known adverse events related to the use of the drug - Leucocytes count15 days

Total leucocyte as CBC x10e)/L

Evaluation of known adverse events related to the use of the drug - Leucocytes formula15 days

formula % on total leucocyte

Evaluation of the epidemiological parameters: Chest CT15 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 Chest15 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-ray15 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 treatment15 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 therapy15 days

Number of AE grade 1 to 4

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