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

Phase 2

Completed

Lead Sponsor: Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia

Brief Summary: 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

Detailed Description: 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

Recruitment & Eligibility

Inclusion Criteria

Acceptance of participation in the study by the patient or legal representative.
Patients of any gender, 18 years or older.
Confirmed diagnosis by PCR+ of SARS-CoV-2 infection.
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.
Levels of IL-6 ≥ 3 times the upper limit of normality

Exclusion Criteria

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

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo + standard therapy
Defibrotide + standard therapy	Defibrotide	Defibrotide + standard therapy

Primary Outcome Measures

Name	Time	Method
Clinical improvement.	7,15, 30 day	Number of days that the patient maintains the clinical improvement. The patient achieves a change of al least 1 category on WHO scale.

Secondary Outcome Measures

Name	Time	Method
Clinical improvement by NEWS2 scales	7, 15, 30 and 60 Day	Decrease ventilation days in grade 6 patients
Radiological response	7, 15, 30 and 60 Day	Improvement of radiological images by conventional radiology
1. Mortality rate	: up to 30 days	All cause mortality
Biologic response	7, 15, 30 and 60 Day	Normal Ferritin or decrease of 50% with respect to the baseline
Collection and storage of biological samples	15,30 days	improve the knowledge of the disease at the inclusion of the patients
Rate os serious adverse events .	7, 15, 30 and 60 Day	Number of adverse events with possible, probable or definite relationship with the study.
Clinical improvement by WHO	7, 15, 30 and 60 Day	Decrease the rate of grades 4-5 patients requiring mechanical ventilation.

Locations (6): Hospital General Universitario Santa Lucía
🇪🇸
Cartagena, Murcia, Spain
Hospital Clinico y Provincial de Barcelona
🇪🇸
Barcelona, Spain
Virgen de la Arrixaca University Clinical Hospital
🇪🇸
Murcia, Spain
Hospital General Universitario Reina Sofía
🇪🇸
Murcia, Spain
Hospital General Universitario Morales Meseguer
🇪🇸
Murcia, Spain
Hospital Universitario Salamanca
🇪🇸
Salamanca, Spain