Clinical trial NCT04361903: Ruxolitinib for the Treatment of Acute Respiratory Distress Syndrome in Patients With COVID-19 Infection
Official title: COVID-19: Ruxolitinib for the Treatment of cytokinE Storm resPiratory dIstREss Syndrome. RESPIRE Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Severe Acute Respiratory Syndrome Coronavirus 2
Keywords: Ruxolitinib
Acute Respiratory Distress Syndrome
COVID-19
Lead sponsor: Azienda USL Toscana Nord Ovest
Sponsor class: OTHER
Collaborators: name: Fondazione C.N.R./Regione Toscana "G. Monasterio", Pisa, Italy
name: Azienda Ospedaliera Universitaria Senese
name: Azienda Ospedaliero, Universitaria Pisana
First posted: 2020-04-24
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of patients who avoid mechanical assisted ventilation in acute respiratory distress syndrome in patients with SARS-CoV-2 COVID-19
timeFrame: 15 days
Secondary outcomes:
measure: Improvement of respiratory performance - Arterial Blood Gas Analisys - pH
timeFrame: 15 days
measure: Improvement of respiratory performance - Arterial Blood Gas Analisys - pO2
timeFrame: 15 days
measure: Improvement of respiratory performance - Arterial Blood Gas Analisys - pCO2
timeFrame: 15 days
measure: Improvement of respiratory performance - ratio values
timeFrame: 15 days
measure: Evaluation of known adverse events related to the use of the drug - D-Dimer
timeFrame: 15 days
measure: Evaluation of known adverse events related to the use of the drug - fibrinogen
timeFrame: 15 days
measure: Evaluation of known adverse events related to the use of the drug - transaminases
timeFrame: 15 days
measure: Evaluation of known adverse events related to the use of the drug - aPTT
timeFrame: 15 days
measure: Evaluation of known adverse events related to the use of the drug - INR
timeFrame: 15 days
measure: Evaluation of known adverse events related to the use of the drug - glycemia
timeFrame: 15 days
measure: Evaluation of known adverse events related to the use of the drug - creatinine
timeFrame: 15 days
measure: Evaluation of known adverse events related to the use of the drug - Leucocytes count
timeFrame: 15 days
measure: Evaluation of known adverse events related to the use of the drug - Leucocytes formula
timeFrame: 15 days
measure: Evaluation of the epidemiological parameters: Chest CT
timeFrame: 15 days
measure: Evaluation of the epidemiological parameters: Eco Chest
timeFrame: 15 days
measure: Evaluation of the epidemiological parameters: CHEST X-ray
timeFrame: 15 days
measure: Monitoring of Serum levels of cytokines before and every 48 h from start to to end of treatment
timeFrame: 15 days
measure: Monitoring incidence of treatment Emergent Adverse Events of ruxolitinib therapy
timeFrame: 15 days
Other outcomes:
Locations:
Study officials:
affiliation: Azienda USL Toscana Nord Ovest
name: Enrico Dr Capochiani, hematologist
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.