COVID19
Conditions
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
Interventions
DRUGDefibrotide
6.25 mg/kg every 6 hours in 2 hours infusion for 7 or 15 days
DRUGPlacebo
Placebo 250 cc every 6 hours for 7 or15 days
Sponsors
Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
double blind
Intervention model description
Phase IIb prospective, multi-center, randomized, parallel, double blind, placebo controlled
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 ventilation days in grade 6 patients |
| Clinical improvement by NEWS2 scales | 7, 15, 30 and 60 Day | Decrease the rate of grades 4-5 patients requiring mechanical ventilation. |
| 1. Mortality rate | : up to 30 days | All cause mortality |
| Radiological response | 7, 15, 30 and 60 Day | Improvement of radiological images by conventional radiology |
| Collection and storage of biological samples | 15,30 days | improve the knowledge of the disease at the inclusion of the patients |
| Biologic response | 7, 15, 30 and 60 Day | Decrease of IL-6 levels with respect to the basal ones \> 50%. |
Countries
Spain
Outcome results
None listed