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

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

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.

Study Overview

• Status: Unknown
• Conditions: Severe Acute Respiratory Syndrome Coronavirus 2
• Intervention / Treatment: Drug: Ruxolitinib Oral Tablet

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.

• Study Type: Observational
• Enrollment (Anticipated): 13

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with SARS-CoV-2 COVID-19 pneumonia who started off-label ruxolitinib treatment in the period between 03/24/2020 and 07/04/2020, with a dosage of at least 20 mg x 2 / day in the first 48 hours

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients treated with ruxolutinib; SARS-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.	Drug: Ruxolitinib Oral Tablet; Ruxolitinib Oral Tablet dosage of at least 20 mg x 2 / day in the first 48 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
Evaluation of known adverse events related to the use of the drug - fibrinogen	every 24 hours fibrinogen value in mg/dl	15 days
Evaluation of known adverse events related to the use of the drug - transaminases	every 24 hours transaminases value in U/L	15 days
Evaluation of known adverse events related to the use of the drug - aPTT	every 24 hours aPTT value in seconds	15 days
Evaluation of known adverse events related to the use of the drug - INR	every 24 hours INR value in %	15 days
Evaluation of known adverse events related to the use of the drug - glycemia	every 24 hours glycemia value in mg/dl	15 days
Evaluation of known adverse events related to the use of the drug - creatinine	every 24 hours creatinine serum value in mg/dl	15 days
Evaluation of known adverse events related to the use of the drug - Leucocytes count	Total leucocyte as CBC x10e)/L	15 days
Evaluation of known adverse events related to the use of the drug - Leucocytes formula	formula % on total leucocyte	15 days
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
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
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
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
Monitoring incidence of treatment Emergent Adverse Events of ruxolitinib therapy	Number of AE grade 1 to 4	15 days

Collaborators and Investigators

• Sponsor: Azienda USL Toscana Nord Ovest
• Collaborators: Azienda Ospedaliero, Universitaria Pisana; Azienda Ospedaliera Universitaria Senese; Fondazione C.N.R./Regione Toscana "G. Monasterio", Pisa, Italy
• Investigators: Principal Investigator: Enrico Dr Capochiani, hematologist, Azienda USL Toscana Nord Ovest

Publications and helpful links

General Publications

• Capochiani E, Frediani B, Iervasi G, Paolicchi A, Sani S, Roncucci P, Cuccaro A, Franchi F, Simonetti F, Carrara D, Bertaggia I, Nasso D, Riccioni R, Scolletta S, Valente S, Conticini E, Gozzetti A, Bocchia M. Ruxolitinib Rapidly Reduces Acute Respiratory Distress Syndrome in COVID-19 Disease. Analysis of Data Collection From RESPIRE Protocol. Front Med (Lausanne). 2020 Aug 4;7:466. doi: 10.3389/fmed.2020.00466. eCollection 2020.

Study record dates

Study Major Dates

• Study Start (Anticipated): April 25, 2020
• Primary Completion (Anticipated): May 24, 2020
• Study Completion (Anticipated): May 31, 2020

Study Registration Dates

• First Submitted: April 14, 2020
• First Submitted That Met QC Criteria: April 23, 2020
• First Posted (Actual): April 24, 2020

Study Record Updates

• Last Update Posted (Actual): April 24, 2020
• Last Update Submitted That Met QC Criteria: April 23, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Ruxolitinib; COVID-19; Acute Respiratory Distress Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease; Infant, Newborn, Diseases; Infant, Premature, Diseases; Severe Acute Respiratory Syndrome; COVID-19; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn
• Other Study ID Numbers: 2020.COVID-19.RUXO106

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No