DEFACOVID: Defibrotide as Prevention and Treatment of Respiratory Distress and Cytokine Release Syndrome of Covid 19.
Study Details
Study Description
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Defibrotide + standard therapy Defibrotide + standard therapy |
Drug: Defibrotide
6.25 mg/kg every 6 hours in 2 hours infusion for 7 or 15 days
|
| Placebo Comparator: Placebo Placebo + standard therapy |
Drug: Placebo
Placebo 250 cc every 6 hours for 7 or15 days
|
Outcome Measures
Primary Outcome Measures
- 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
- 1. Mortality rate [: up to 30 days]
All cause mortality
- 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.
- Clinical improvement by NEWS2 scales [7, 15, 30 and 60 Day]
Decrease ventilation days in grade 6 patients
- Biologic response [7, 15, 30 and 60 Day]
Decrease of IL-6 levels with respect to the basal ones > 50%.
- Biologic response [7, 15, 30 and 60 Day]
Absolute lymphocytes count: 50% increase with respect to the baseline
- Biologic response [7, 15, 30 and 60 Day]
Normal D-dimer (DD) or decrease of 50% with respect to the baseline
- Biologic response [7, 15, 30 and 60 Day]
Normal CRP or decrease of 50% with respect to the baseline
- Biologic response [7, 15, 30 and 60 Day]
Normal LDH or decrease of 50% with respect to the baseline
- Biologic response [7, 15, 30 and 60 Day]
Normal CPK or decrease of 50% with respect to the baseline
- Biologic response [7, 15, 30 and 60 Day]
Normal Ferritin or decrease of 50% with respect to the baseline
- 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
- Clinical improvement by WHO [7, 15, 30 and 60 Day]
Decrease the rate of grades 4-5 patients requiring mechanical ventilation.
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hospital General Universitario Santa Lucía | Cartagena | Murcia | Spain | |
| 2 | Hospital Clinico y Provincial de Barcelona | Barcelona | Spain | ||
| 3 | Hospital Fundación Jiménez Díaz | Madrid | Spain | ||
| 4 | Hospital Universitario 12 de Octubre | Madrid | Spain | ||
| 5 | Virgen de la Arrixaca University Clinical Hospital | Murcia | Spain | 30120 | |
| 6 | Hospital General Universitario Morales Meseguer | Murcia | Spain | ||
| 7 | Hospital General Universitario Reina Sofía | Murcia | Spain | ||
| 8 | Hospital Universitario Salamanca | Salamanca | Spain |
Sponsors and Collaborators
- Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IMIB-DFC-2020-02