Personalised Immunotherapy for SARS-CoV-2 (COVID-19) Associated With Organ Dysfunction (ESCAPE)
COVID-19, Virus Diseases, Macrophage Activation Syndrome
About this trial
This is an interventional treatment trial for COVID-19 focused on measuring COVID-19, SARS-CoV-2, MAS, Anakinra, Tocilizumab
Eligibility 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
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
Sites / Locations
- 2nd Department of Critical Care Medicine, ATTIKON University Hospital
- Intensive Care Unit, Ioannina University Hospital
- Department of Internal Medicine, Patras University Hospital
- Department of Internal Medicine, I PAMMAKARISTOS Hospital
- Intensive Care Unit, General Hospital of Athens KORGIALENIO-BENAKIO E.E.S.
- 1st Department of Pulmonary Medicine and Intensive Care Unit
- Intensive Care Unit, General Hospital of Athens IPPOKRATEIO
- 4th Department of Internal Medicine, Attikon University Hospital
- Intensive Care Unit, General Hospital ASKLEPIEIO Voulas
- Intensive Care Unit, "Latsio", Thriasio Elefsis General Hospital
- Intensive Care Unit, "Koutlimbaneio & Triantafylleio" Larissa General Hospital
- Department of Internal Medicine, Larissa University Hospital
- Intensive Care Unit, AGIOS DIMITRIOS General Hospital of Thessaloniki
- Intensive Care Unit, G. GENNIMATAS General Hospital of Thessaloniki
- Intensive Care Unit, Theageneio Oncological Hospital of Thessaloniki
- Intensive Care Unit, General Hospital of Thessaloniki IPPOKRATEIO
- Department of Anesthesiology and Intensive Care Medicine, University General Hospital of Thessaloniki AHEPA
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
anakinra
tocilizumab
In case of diagnosis of MAS, IV anakinra 200mg three times daily (every eight hours) for 7 days. Patients who will receive anakinra treatment and who suffer from kidney dysfunction will receive 50% of the dose i.e. 100mg anakinra three times daily for 15 days
In case of diagnosis of immune dysregulation IV tocilizumab 8mg/kg body weight once up to a maximum of 800mg. These patients will receive anakinra at the above dose in case they meet one of the following contra-indications for tocilizumab: absolute neutrophil count less than 2,500/mm3; absolute platelet count less than 100,000/mm3; and AST or ALT more than 1.5 x the upper normal limit