Defibrotide as Prevention and Treatment of Respiratory Distress and Cytokine Release Syndrome of Covid 19.

Phase IIb Prospective, Multi-center, Randomized, Parallel, Double Blind, Placebo Controlled Trial to Evaluate Defibrotide Intravenous Infusion in the Prevention and Treatment of COVID-19 Respiratory Distress and Cytokine Release Syndrome

Protection of endothelial dysfunction by intravenous infusion of Defibrotide (Defitelio), expected to decrease inflammation and expression of adhesion molecules in the endothelium, leukocyte tissue infiltration and epithelial destruction, and to promote immune tolerance through a change in the Cytokine balance, which is decisive in preventing multiorgan failure and death in patients with SARS-CoV-2 infection with clinical status grade 4 or 5 according to the WHO classification

Protection of endothelial dysfunction by intravenous infusion of Defibrotide (Defitelio), expected to decrease inflammation and expression of adhesion molecules in the endothelium, leukocyte tissue infiltration and epithelial destruction, and to promote immune tolerance through a change in the Cytokine balance, which is decisive in preventing multiorgan failure and death in patients with SARS-CoV-2 infection with clinical status grade 4 or 5 according to the WHO classification

Inclusion Criteria:

1. Acceptance of participation in the study by the patient or legal representative.

2. Patients of any gender, 18 years or older.

3. Confirmed diagnosis by PCR+ of SARS-CoV-2 infection.

4. COVID-19 positive patients WHO grades 4, 5 or 6.

   • Grade 4: hospitalized requiring oxygen therapy.
   • Grade 5: hospitalized requiring high-flow oxygen therapy, noninvasive mechanical ventilation, or both.

5. Levels of IL-6 ≥ 3 times the upper limit of normality

Exclusion Criteria:

1. Acute bleeding.
2. Thrombolytic treatment and anticoagulant treatment at therapeutic doses.
3. Pregnancy or lactation.
4. Patients with active malignant tumour, other serious systemic or neuropsychiatric diseases.
5. Patients participating in other clinical trials in the last month.
6. Inability to give informed consent or to accomplish the requirements of the diagnostic tests.
7. Patients with hypersensitivity to Defibrotide.