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

COVID19 Clinical Trial

— DEFACOVID  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04348383
• Other study ID #: IMIB-DFC-2020-02
• Status: Completed
• Phase: Phase 2
• Start date: April 8, 2020
• Est. completion date: February 28, 2023

Study information

• Verified date: June 2022
• Source: Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Completed
• Enrollment: 156
• Est. completion date: February 28, 2023
• Est. primary completion date: February 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19
• COVID19
• Cytokine Release Syndrome

Intervention

Drug:
• Defibrotide
6.25 mg/kg every 6 hours in 2 hours infusion for 7 or 15 days
• Placebo
Placebo 250 cc every 6 hours for 7 or15 days

Locations

Country	Name	City	State
Spain	Hospital Clinico y Provincial de Barcelona	Barcelona
Spain	Hospital General Universitario Santa Lucía	Cartagena	Murcia
Spain	Hospital General Universitario Morales Meseguer	Murcia
Spain	Hospital General Universitario Reina Sofía	Murcia
Spain	Virgen de la Arrixaca University Clinical Hospital	Murcia
Spain	Hospital Universitario Salamanca	Salamanca

Sponsors (1)

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

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical improvement.	Number of days that the patient maintains the clinical improvement. The patient achieves a change of al least 1 category on WHO scale.	7,15, 30 day
Secondary	1. Mortality rate	All cause mortality	: up to 30 days
Secondary	Rate os serious adverse events .	Number of adverse events with possible, probable or definite relationship with the study.	7, 15, 30 and 60 Day
Secondary	Clinical improvement by WHO	Decrease ventilation days in grade 6 patients	7, 15, 30 and 60 Day
Secondary	Clinical improvement by NEWS2 scales	Decrease the rate of grades 4-5 patients requiring mechanical ventilation.	7, 15, 30 and 60 Day
Secondary	Clinical improvement by NEWS2 scales	Decrease ventilation days in grade 6 patients	7, 15, 30 and 60 Day
Secondary	Biologic response	Decrease of IL-6 levels with respect to the basal ones > 50%.	7, 15, 30 and 60 Day
Secondary	Biologic response	Absolute lymphocytes count: 50% increase with respect to the baseline	7, 15, 30 and 60 Day
Secondary	Biologic response	Normal D-dimer (DD) or decrease of 50% with respect to the baseline	7, 15, 30 and 60 Day
Secondary	Biologic response	Normal CRP or decrease of 50% with respect to the baseline	7, 15, 30 and 60 Day
Secondary	Biologic response	Normal LDH or decrease of 50% with respect to the baseline	7, 15, 30 and 60 Day
Secondary	Biologic response	Normal CPK or decrease of 50% with respect to the baseline	7, 15, 30 and 60 Day
Secondary	Biologic response	Normal Ferritin or decrease of 50% with respect to the baseline	7, 15, 30 and 60 Day
Secondary	Radiological response	Improvement of radiological images by conventional radiology	7, 15, 30 and 60 Day
Secondary	Collection and storage of biological samples	improve the knowledge of the disease at the inclusion of the patients	15,30 days
Secondary	Clinical improvement by WHO	Decrease the rate of grades 4-5 patients requiring mechanical ventilation.	7, 15, 30 and 60 Day