Organ dysfunction by the novel SARS-Cov-2 virus MedDRA version: 20.0 Level: LLT Classification code 10035738 Term: Pneumonia viral NOS System Organ Class: 100000004862
Conditions
Interventions
Trade Name: Kineret
Product Name: Anakinra
Pharmaceutical Form:
Trade Name: RoActemra
Product Name: Tocilizumab
Pharmaceutical Form: Concentrate for solution for infusion
Sponsors
HELLENIC INSTITUTE FOR THE STUDY OF SEPSIS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age equal to or above 18 years • Male or female gender • In case of women, unwillingness to remain pregnant during the study period. • Written informed consent provided by the patient or by one first-degree relative/spouse in case of patients unable to consent • Confirmed infection by SARS-CoV-2 virus using molecular techniques as defined by the World Health Organization11 • Organ dysfunction defined as the presence of at least one of the following conditions: - Total SOFA score greater than or equal to 2; - Involvement of the lower respiratory tract • Laboratory documentation of MAS or immune dysregulation. MAS is documented by the findings of any serum ferritin greater than 4,420ng/ml. immune dysregulation is documented by the combination of two findings: a) serum ferritin equal to or lower than 4,420ng/ml; and b) less than 5,000 receptors of the membrane molecule of HLA-DR on the cell membrane of blood CD14-monocytes or less than 30 MFI of HLA-DR on the cell membrane of blood CD14-monocytes as counted by flow cytometry. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: • Age below 18 years • Denial for written informed consent • Any stage IV malignancy • Any do not resuscitate decision • Active tuberculosis (TB) as defined by the co-administration of drugs for the treatment of TB • Infection by the human immunodeficiency virus (HIV) • Any primary immunodeficiency • Oral or IV intake of corticosteroids at a daily dose equal or greater than 0.4 mg prednisone or greater the last 15 days. • Any anti-cytokine biological treatment the last one month • Medical history of systemic lupus erythematosus • Medical history of multiple sclerosis or any other demyelinating disorder. • Pregnancy or lactation. Women of child-bearing potential will be screened by a urine pregnancy test before inclusion in the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Our aim is to conduct one trial of personalized immunotherapy in patients with SARS-CoV-2 associated with organ dysfunction and with laboratory findings of macrophage activation syndrome or immune dysregulation. These patients will be selected by the use of a panel of biomarkers and laboratory findings and they will be allocated to immunotherapy treatment according to their needs. ;Secondary Objective: Not applicable;Primary end point(s): The study primary endpoint is composite and contains the achievement of at least one of the following goals or both goals after 7 days (study visit of day 8): • At least 25% decrease of baseline total SOFA score or increase of the pO2/FiO2 ratio by at least 50% • Clinical improvement of lung involvement Patients discharged from hospital alive before study visit of day 8 are considered achieving the primary endpoint. Patients dying before study visit of day 8 are considered non-achieving the primary endpoint.;Timepoint(s) of evaluation of this end point: Visit study day 8 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Comparison of the primary endpoint with historical comparators • Change of SOFA score on day 28 • Mortality on day 28 • Mortality on day 90 • Change of cytokine stimulation between days 0 and 4 • Change of gene expression between days 0 and 4 • Change of serum/plasma proteins between days 0 and 4 • Classification of immune function of screened patients who are not enrolled in study drug since they do not have MAS or immune dysregulation The above secondary endpoints will also be analyzed separately to study the specific effect of anakinra and of tocilizumab.;Timepoint(s) of evaluation of this end point: Screening Day 4 Day 15 Day 28 Day 90 | — |
Countries
Greece
Contacts
Public ContactPresident of the Board
HELLENIC INSTITUTE FOR THE STUDY OF SEPSIS
Outcome results
None listed