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

Primary Purpose

COVID19

Status
Completed
Phase
Phase 2
Locations
Spain
Study Type
Interventional
Intervention
Defibrotide
Placebo
Sponsored by
Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COVID19

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Hospital General Universitario Santa Lucía
  • Hospital Clinico y Provincial de Barcelona
  • Virgen de la Arrixaca University Clinical Hospital
  • Hospital General Universitario Morales Meseguer
  • Hospital General Universitario Reina Sofía
  • Hospital Universitario Salamanca

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Defibrotide + standard therapy

Placebo

Arm Description

Defibrotide + standard therapy

Placebo + standard therapy

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

1. Mortality rate
All cause mortality
Rate os serious adverse events .
Number of adverse events with possible, probable or definite relationship with the study.
Clinical improvement by WHO
Decrease ventilation days in grade 6 patients
Clinical improvement by NEWS2 scales
Decrease the rate of grades 4-5 patients requiring mechanical ventilation.
Clinical improvement by NEWS2 scales
Decrease ventilation days in grade 6 patients
Biologic response
Decrease of IL-6 levels with respect to the basal ones > 50%.
Biologic response
Absolute lymphocytes count: 50% increase with respect to the baseline
Biologic response
Normal D-dimer (DD) or decrease of 50% with respect to the baseline
Biologic response
Normal CRP or decrease of 50% with respect to the baseline
Biologic response
Normal LDH or decrease of 50% with respect to the baseline
Biologic response
Normal CPK or decrease of 50% with respect to the baseline
Biologic response
Normal Ferritin or decrease of 50% with respect to the baseline
Radiological response
Improvement of radiological images by conventional radiology
Collection and storage of biological samples
improve the knowledge of the disease at the inclusion of the patients
Clinical improvement by WHO
Decrease the rate of grades 4-5 patients requiring mechanical ventilation.

Full Information

First Posted
April 8, 2020
Last Updated
June 6, 2023
Sponsor
Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia
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1. Study Identification

Unique Protocol Identification Number
NCT04348383
Brief Title
Defibrotide as Prevention and Treatment of Respiratory Distress and Cytokine Release Syndrome of Covid 19.
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
April 8, 2020 (Actual)
Primary Completion Date
February 28, 2023 (Actual)
Study Completion Date
February 28, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No

5. 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
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID19

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Phase IIb prospective, multi-center, randomized, parallel, double blind, placebo controlled
Masking
ParticipantInvestigator
Masking Description
double blind
Allocation
Randomized
Enrollment
156 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Defibrotide + standard therapy
Arm Type
Experimental
Arm Description
Defibrotide + standard therapy
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo + standard therapy
Intervention Type
Drug
Intervention Name(s)
Defibrotide
Intervention Description
6.25 mg/kg every 6 hours in 2 hours infusion for 7 or 15 days
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo 250 cc every 6 hours for 7 or15 days
Primary Outcome Measure Information:
Title
Clinical improvement.
Description
Number of days that the patient maintains the clinical improvement. The patient achieves a change of al least 1 category on WHO scale.
Time Frame
7,15, 30 day
Secondary Outcome Measure Information:
Title
1. Mortality rate
Description
All cause mortality
Time Frame
: up to 30 days
Title
Rate os serious adverse events .
Description
Number of adverse events with possible, probable or definite relationship with the study.
Time Frame
7, 15, 30 and 60 Day
Title
Clinical improvement by WHO
Description
Decrease ventilation days in grade 6 patients
Time Frame
7, 15, 30 and 60 Day
Title
Clinical improvement by NEWS2 scales
Description
Decrease the rate of grades 4-5 patients requiring mechanical ventilation.
Time Frame
7, 15, 30 and 60 Day
Title
Clinical improvement by NEWS2 scales
Description
Decrease ventilation days in grade 6 patients
Time Frame
7, 15, 30 and 60 Day
Title
Biologic response
Description
Decrease of IL-6 levels with respect to the basal ones > 50%.
Time Frame
7, 15, 30 and 60 Day
Title
Biologic response
Description
Absolute lymphocytes count: 50% increase with respect to the baseline
Time Frame
7, 15, 30 and 60 Day
Title
Biologic response
Description
Normal D-dimer (DD) or decrease of 50% with respect to the baseline
Time Frame
7, 15, 30 and 60 Day
Title
Biologic response
Description
Normal CRP or decrease of 50% with respect to the baseline
Time Frame
7, 15, 30 and 60 Day
Title
Biologic response
Description
Normal LDH or decrease of 50% with respect to the baseline
Time Frame
7, 15, 30 and 60 Day
Title
Biologic response
Description
Normal CPK or decrease of 50% with respect to the baseline
Time Frame
7, 15, 30 and 60 Day
Title
Biologic response
Description
Normal Ferritin or decrease of 50% with respect to the baseline
Time Frame
7, 15, 30 and 60 Day
Title
Radiological response
Description
Improvement of radiological images by conventional radiology
Time Frame
7, 15, 30 and 60 Day
Title
Collection and storage of biological samples
Description
improve the knowledge of the disease at the inclusion of the patients
Time Frame
15,30 days
Title
Clinical improvement by WHO
Description
Decrease the rate of grades 4-5 patients requiring mechanical ventilation.
Time Frame
7, 15, 30 and 60 Day

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Facility Information:
Facility Name
Hospital General Universitario Santa Lucía
City
Cartagena
State/Province
Murcia
Country
Spain
Facility Name
Hospital Clinico y Provincial de Barcelona
City
Barcelona
Country
Spain
Facility Name
Virgen de la Arrixaca University Clinical Hospital
City
Murcia
ZIP/Postal Code
30120
Country
Spain
Facility Name
Hospital General Universitario Morales Meseguer
City
Murcia
Country
Spain
Facility Name
Hospital General Universitario Reina Sofía
City
Murcia
Country
Spain
Facility Name
Hospital Universitario Salamanca
City
Salamanca
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
No

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

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