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

Severe Acute Respiratory Syndrome Coronavirus 2 Clinical Trial

— RESPIRE  

Official title:

COVID-19: Ruxolitinib for the Treatment of cytokinE Storm resPiratory dIstREss Syndrome. RESPIRE Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04361903
• Other study ID #: 2020.COVID-19.RUXO106
• Status: Not yet recruiting
• Start date: April 25, 2020
• Est. completion date: May 31, 2020

Study information

• Verified date: April 2020
• Source: Azienda USL Toscana Nord Ovest
• Contact: Enrico Dr Capochiani, hematologist
• Phone: 00393473527340
• Email: enrico.capochiani[@]uslnordovest.toscana.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Not yet recruiting
• Enrollment: 13
• Est. completion date: May 31, 2020
• Est. primary completion date: May 24, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Coronavirus Infections
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn
• Severe Acute Respiratory Syndrome
• Severe Acute Respiratory Syndrome Coronavirus 2
• Syndrome

Intervention

Drug:
• Ruxolitinib Oral Tablet
Ruxolitinib Oral Tablet dosage of at least 20 mg x 2 / day in the first 48 hours

Locations

Country	Name	City	State
n/a

Sponsors (4)

Lead Sponsor	Collaborator
Azienda USL Toscana Nord Ovest	Azienda Ospedaliera Universitaria Senese, Azienda Ospedaliero, Universitaria Pisana, Fondazione C.N.R./Regione Toscana "G. Monasterio", Pisa, Italy

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients who avoid mechanical assisted ventilation in acute respiratory distress syndrome in patients with SARS-CoV-2 COVID-19	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	15 days
Secondary	Improvement of respiratory performance - Arterial Blood Gas Analisys - pH	ABG (arterial Blood Gas): pH as SI Unit, every 12 hours and in any case in the presence of significant clinical variations.	15 days
Secondary	Improvement of respiratory performance - Arterial Blood Gas Analisys - pO2	ABG (arterial Blood Gas): pO2 in mm Hg, every 12 hours and in any case in the presence of significant clinical variations.	15 days
Secondary	Improvement of respiratory performance - Arterial Blood Gas Analisys - pCO2	ABG (arterial Blood Gas): pCO2 in mm Hg, every 12 hours and in any case in the presence of significant clinical variations.	15 days
Secondary	Improvement of respiratory performance - ratio values	PaO2 / FiO2, SatO2 ratio. Vital parameters and respiratory function every 12 hours and in any case in the presence of significant clinical variations.	15 days
Secondary	Evaluation of known adverse events related to the use of the drug - D-Dimer	every 24 hours D-Dimer value in mgr/ml	15 days
Secondary	Evaluation of known adverse events related to the use of the drug - fibrinogen	every 24 hours fibrinogen value in mg/dl	15 days
Secondary	Evaluation of known adverse events related to the use of the drug - transaminases	every 24 hours transaminases value in U/L	15 days
Secondary	Evaluation of known adverse events related to the use of the drug - aPTT	every 24 hours aPTT value in seconds	15 days
Secondary	Evaluation of known adverse events related to the use of the drug - INR	every 24 hours INR value in %	15 days
Secondary	Evaluation of known adverse events related to the use of the drug - glycemia	every 24 hours glycemia value in mg/dl	15 days
Secondary	Evaluation of known adverse events related to the use of the drug - creatinine	every 24 hours creatinine serum value in mg/dl	15 days
Secondary	Evaluation of known adverse events related to the use of the drug - Leucocytes count	Total leucocyte as CBC x10e)/L	15 days
Secondary	Evaluation of known adverse events related to the use of the drug - Leucocytes formula	formula % on total leucocyte	15 days
Secondary	Evaluation of the epidemiological parameters: Chest CT	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.	15 days
Secondary	Evaluation of the epidemiological parameters: Eco Chest	Thoracic imaging: every day: presence and number of line B every 48 hours.Time elapsed between the onset of clinical symptoms and hospitalization.	15 days
Secondary	Evaluation of the epidemiological parameters: CHEST X-ray	Thoracic imaging: presence, extension and dimension on lung thickening - Chest X-ray, Time elapsed between the onset of clinical symptoms and hospitalization.	15 days
Secondary	Monitoring of Serum levels of cytokines before and every 48 h from start to to end of treatment	Monitoring of serum cytokines (IL-6 in pgr/dL, TNF in pgr/dL) every 48 h	15 days
Secondary	Monitoring incidence of treatment Emergent Adverse Events of ruxolitinib therapy	Number of AE grade 1 to 4	15 days