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

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ClinicalTrials.gov Identifier: NCT04348383
Recruitment Status : Recruiting
First Posted : April 16, 2020
Last Update Posted : February 9, 2021
Sponsor:
Information provided by (Responsible Party):
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, 5 or 6 according to the WHO classification

Condition or disease Intervention/treatment Phase
COVID19 Drug: Defibrotide 25 mg/kg 24 hours continuous infusion for 15 days Drug: Placebo 250 cc 24 hours continuous infusion for 15 days 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, 5 or 6 according to the WHO classification

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Phase IIb prospective, multi-center, randomized, parallel, double blind, placebo controlled
Masking: Double (Participant, Investigator)
Masking Description: double blind
Primary Purpose: Treatment
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
Actual Study Start Date : April 8, 2020
Estimated Primary Completion Date : April 15, 2021
Estimated Study Completion Date : May 15, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Defibrotide + standard therapy
Defibrotide + standard therapy
Drug: Defibrotide 25 mg/kg 24 hours continuous infusion for 15 days
Defibrotide 25 mg/kg 24 hours continuous infusion for 15 days

Placebo Comparator: Placebo
Placebo + standard therapy
Drug: Placebo 250 cc 24 hours continuous infusion for 15 days
Placebo 250 cc 24 hours continuous infusion for 15 days




Primary Outcome Measures :
  1. Clinical improvement. [ Time Frame: 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. 1. Mortality rate [ Time Frame: : up to 30 days ]
    All cause mortality

  2. Rate os serious adverse events . [ Time Frame: 7, 15, 30 and 60 Day ]
    Number of adverse events with possible, probable or definite relationship with the study.

  3. Clinical improvement by WHO [ Time Frame: 7, 15, 30 and 60 Day ]
    Decrease ventilation days in grade 6 patients

  4. Clinical improvement by NEWS2 scales [ Time Frame: 7, 15, 30 and 60 Day ]
    Decrease the rate of grades 4-5 patients requiring mechanical ventilation.

  5. Clinical improvement by NEWS2 scales [ Time Frame: 7, 15, 30 and 60 Day ]
    Decrease ventilation days in grade 6 patients

  6. Biologic response [ Time Frame: 7, 15, 30 and 60 Day ]
    Decrease of IL-6 levels with respect to the basal ones > 50%.

  7. Biologic response [ Time Frame: 7, 15, 30 and 60 Day ]
    Absolute lymphocytes count: 50% increase with respect to the baseline

  8. Biologic response [ Time Frame: 7, 15, 30 and 60 Day ]
    Normal D-dimer (DD) or decrease of 50% with respect to the baseline

  9. Biologic response [ Time Frame: 7, 15, 30 and 60 Day ]
    Normal CRP or decrease of 50% with respect to the baseline

  10. Biologic response [ Time Frame: 7, 15, 30 and 60 Day ]
    Normal LDH or decrease of 50% with respect to the baseline

  11. Biologic response [ Time Frame: 7, 15, 30 and 60 Day ]
    Normal CPK or decrease of 50% with respect to the baseline

  12. Biologic response [ Time Frame: 7, 15, 30 and 60 Day ]
    Normal Ferritin or decrease of 50% with respect to the baseline

  13. Radiological response [ Time Frame: 7, 15, 30 and 60 Day ]
    Improvement of radiological images by conventional radiology

  14. Collection and storage of biological samples [ Time Frame: 15,30 days ]
    improve the knowledge of the disease at the inclusion of the patients

  15. Clinical improvement by WHO [ Time Frame: 7, 15, 30 and 60 Day ]
    Decrease the rate of grades 4-5 patients requiring mechanical ventilation.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
    • Grade 6: hospitalized requiring ECMO, mechanical ventilation or both.Exclusion Criteria:
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04348383


Contacts
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Contact: José M. Moraleda, MD +34 968369532 jmoraled@um.es

Locations
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Spain
Hospital General Universitario Santa Lucía Recruiting
Cartagena, Murcia, Spain
Contact: Antonio Santa Cruz         
Hospital Clinico y Provincial de Barcelona Recruiting
Barcelona, Spain
Contact: Pedro Castro Rebollo         
Virgen de la Arrixaca University Clinical Hospital Recruiting
Murcia, Spain, 30120
Hospital General Universitario Morales Meseguer Recruiting
Murcia, Spain
Contact: Andres Carrillo, MD         
Hospital General Universitario Reina Sofía Recruiting
Murcia, Spain
Contact: Enrique Bernal Morell         
Hospital Universitario Salamanca Recruiting
Salamanca, Spain
Contact: Amparo López Bernús         
Sponsors and Collaborators
Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia
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Responsible Party: Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia
ClinicalTrials.gov Identifier: NCT04348383    
Other Study ID Numbers: IMIB-DFC-2020-02
First Posted: April 16, 2020    Key Record Dates
Last Update Posted: February 9, 2021
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Additional relevant MeSH terms:
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Defibrotide
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors