Clinical trial NCT04348383: Defibrotide as Prevention and Treatment of Respiratory Distress and Cytokine Release Syndrome of Covid 19.
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: COVID19
Lead sponsor: Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia
Sponsor class: OTHER
First posted: 2020-04-16
Enrollment: 156
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase IIb prospective, multi-center, randomized, parallel, double blind, placebo controlled
Primary purpose: TREATMENT

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

Eligibility 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.
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.

Primary outcomes:
measure: Clinical improvement.
timeFrame: 7,15, 30 day
Secondary outcomes:
measure: 1. Mortality rate
timeFrame: : up to 30 days
measure: Rate os serious adverse events .
timeFrame: 7, 15, 30 and 60 Day
measure: Clinical improvement by WHO
timeFrame: 7, 15, 30 and 60 Day
measure: Clinical improvement by NEWS2 scales
timeFrame: 7, 15, 30 and 60 Day
measure: Clinical improvement by NEWS2 scales
timeFrame: 7, 15, 30 and 60 Day
measure: Biologic response
timeFrame: 7, 15, 30 and 60 Day
measure: Biologic response
timeFrame: 7, 15, 30 and 60 Day
measure: Biologic response
timeFrame: 7, 15, 30 and 60 Day
measure: Biologic response
timeFrame: 7, 15, 30 and 60 Day
measure: Biologic response
timeFrame: 7, 15, 30 and 60 Day
measure: Biologic response
timeFrame: 7, 15, 30 and 60 Day
measure: Biologic response
timeFrame: 7, 15, 30 and 60 Day
measure: Radiological response
timeFrame: 7, 15, 30 and 60 Day
measure: Collection and storage of biological samples
timeFrame: 15,30 days
measure: Clinical improvement by WHO
timeFrame: 7, 15, 30 and 60 Day
Other outcomes:
Locations:
city: Cartagena
country: Spain
facility: Hospital General Universitario Santa Lucía
state: Murcia
city: Barcelona
country: Spain
facility: Hospital Clinico y Provincial de Barcelona
city: Murcia
country: Spain
facility: Virgen de la Arrixaca University Clinical Hospital
city: Murcia
country: Spain
facility: Hospital General Universitario Morales Meseguer
city: Murcia
country: Spain
facility: Hospital General Universitario Reina Sofía
city: Salamanca
country: Spain
facility: Hospital Universitario Salamanca
Study officials:
References: