COVID19Phase 2DEFACOVIDNCT04348383
Defibrotide as Prevention and Treatment of Respiratory Distress and Cytokine Release Syndrome of Covid 19.
A Phase 2 study testing Defibrotide in people with COVID19, run by Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia at 6 sites in Spain.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID19
- What is being tested?
- Defibrotide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 156 participants
- Where
- 6 sitesSpain
- Study dates
- 8 Apr 2020to 28 Feb 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Spain6 sites
Hospital Clinico y Provincial de Barcelona
Barcelona
Hospital General Universitario Santa Lucía
Cartagena, Murcia
Virgen de la Arrixaca University Clinical Hospital
Murcia, 30120
Hospital General Universitario Morales Meseguer
Murcia
Hospital General Universitario Reina Sofía
Murcia
Hospital Universitario Salamanca
Salamanca
About this study
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
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
Read the 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
- Conditions
- COVID19
- Being tested
- Defibrotide, Placebo
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DefibrotideDrug
6.25 mg/kg every 6 hours in 2 hours infusion for 7 or 15 days
PlaceboDrug
Placebo 250 cc every 6 hours for 7 or15 days
| Study group | Role | What they receive |
|---|---|---|
| Defibrotide + standard therapy | Experimental | Defibrotide + standard therapy Receives: Drug: Defibrotide |
| Placebo | Placebo comparator | Placebo + standard therapy Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 7,15, 30 day
Secondary outcomes (15)
1. Mortality rate
All cause mortality
Measured: : up to 30 days
Rate os serious adverse events .
Number of adverse events with possible, probable or definite relationship with the study.
Measured: 7, 15, 30 and 60 Day
Clinical improvement by WHO
Decrease ventilation days in grade 6 patients
Measured: 7, 15, 30 and 60 Day
Clinical improvement by NEWS2 scales
Decrease the rate of grades 4-5 patients requiring mechanical ventilation.
Measured: 7, 15, 30 and 60 Day
Clinical improvement by NEWS2 scales
Decrease ventilation days in grade 6 patients
Measured: 7, 15, 30 and 60 Day
Biologic response
Decrease of IL-6 levels with respect to the basal ones > 50%.
Measured: 7, 15, 30 and 60 Day
Biologic response
Absolute lymphocytes count: 50% increase with respect to the baseline
Measured: 7, 15, 30 and 60 Day
Biologic response
Normal D-dimer (DD) or decrease of 50% with respect to the baseline
Measured: 7, 15, 30 and 60 Day
Biologic response
Normal CRP or decrease of 50% with respect to the baseline
Measured: 7, 15, 30 and 60 Day
Biologic response
Normal LDH or decrease of 50% with respect to the baseline
Measured: 7, 15, 30 and 60 Day
Biologic response
Normal CPK or decrease of 50% with respect to the baseline
Measured: 7, 15, 30 and 60 Day
Biologic response
Normal Ferritin or decrease of 50% with respect to the baseline
Measured: 7, 15, 30 and 60 Day
Radiological response
Improvement of radiological images by conventional radiology
Measured: 7, 15, 30 and 60 Day
Collection and storage of biological samples
improve the knowledge of the disease at the inclusion of the patients
Measured: 15,30 days
Clinical improvement by WHO
Decrease the rate of grades 4-5 patients requiring mechanical ventilation.
Measured: 7, 15, 30 and 60 Day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2020
- Study start8 Apr 2020
- Primary completion28 Feb 2023
- Study completion28 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for COVID19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Phase IIb prospective, multi-center, randomized, parallel, double blind, placebo controlled
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 156 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04348383
- Sponsor's protocol ID
- IMIB-DFC-2020-02
- Acronym
- DEFACOVID
- Status last verified
- Jun 2022
- First submitted
- 8 Apr 2020
- Last updated
- 7 Jun 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Jara Rubio R, Martinez-Mellado AJ, Kiwitt-Cardenas J, Clavel JG, Garcia-Perez B, Castro P, Diaz-Ricart M, Carrillo-Alcaraz A, Lopez-Bernus A, Bernal Morell E, Roura A, Marin S, Ruiz-Lopez FJ, Solana-Martinez E, Martinez-Bano D, Albacete Moreno CL, Andreu Soler E, Tellez Santoyo A, Fernandez Mendez S, Noguera Velasco JA, Cebreiros Lopez I, Parrilla A, Espuny-Miro A, Garcia-Bernal D, Blanquer M, Sanchez-Salinas A, Iniesta F, Hernandez Garcia C, Muro M, Minguela Puras A, Moreno-Docon A, Torres-Cantero AM, Munoz Garcia M, Serrano M, Iacobelli M, Carlo-Stella C, Wei LJ, Richardson PG, Moraleda JM. Phase IIB, Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Intravenous Defibrotide for the Prevention and Treatment of Respiratory Distress and Cytokine Release Syndrome in COVID-19. Eur J Haematol. 2026 May 12. doi: 10.1111/ejh.70214. Online ahead of print.
PubMed 42117493
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04348383
- Acronym / sponsor ID
- DEFACOVID / IMIB-DFC-2020-02
- Conditions
- COVID19
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 156 participants (actual)
- Lead sponsor
- Fundacion para la Formacion e Investigacion Sanitarias de la Region de MurciaUniversity, hospital or other
- Study start
- 8 Apr 2020 (actual)
- Primary completion
- 28 Feb 2023 (actual)
- Study completion
- 28 Feb 2023 (actual)
- First posted
- 16 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Phase IIb prospective, multi-center, randomized, parallel, double blind, placebo controlled
| Arm | Type | Receives |
|---|---|---|
| Defibrotide + standard therapy | Experimental | Drug: DefibrotideDefibrotide + standard therapy |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo + standard therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
- Levels of IL-6 ≥ 3 times the upper limit of normality
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Defibrotide6.25 mg/kg every 6 hours in 2 hours infusion for 7 or 15 days | Drug | Defibrotide + standard therapy |
| PlaceboPlacebo 250 cc every 6 hours for 7 or15 days | Drug | Placebo |
Primary outcome
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.
15 secondary outcomes
1. Mortality rate
Time frame: : up to 30 days
Rate os serious adverse events .
Time frame: 7, 15, 30 and 60 Day
Clinical improvement by WHO
Time frame: 7, 15, 30 and 60 Day
Clinical improvement by NEWS2 scales
Time frame: 7, 15, 30 and 60 Day
Clinical improvement by NEWS2 scales
Time frame: 7, 15, 30 and 60 Day
Biologic response
Time frame: 7, 15, 30 and 60 Day
Biologic response
Time frame: 7, 15, 30 and 60 Day
Biologic response
Time frame: 7, 15, 30 and 60 Day
Biologic response
Time frame: 7, 15, 30 and 60 Day
Biologic response
Time frame: 7, 15, 30 and 60 Day
Biologic response
Time frame: 7, 15, 30 and 60 Day
Biologic response
Time frame: 7, 15, 30 and 60 Day
Radiological response
Time frame: 7, 15, 30 and 60 Day
Collection and storage of biological samples
Time frame: 15,30 days
Clinical improvement by WHO
Time frame: 7, 15, 30 and 60 Day
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2023.
- Derived from this study: PubMed 42117493Jara Rubio R, Martinez-Mellado AJ, Kiwitt-Cardenas J, Clavel JG, Garcia-Perez B, Castro P, Diaz-Ricart M, Carrillo-Alcaraz A, Lopez-Bernus A, Bernal Morell E, Roura A, Marin S, Ruiz-Lopez FJ, Solana-Martinez E, Martinez-Bano D, Albacete Moreno CL, Andreu Soler E, Tellez Santoyo A, Fernandez Mendez S, Noguera Velasco JA, Cebreiros Lopez I, Parrilla A, Espuny-Miro A, Garcia-Bernal D, Blanquer M, Sanchez-Salinas A, Iniesta F, Hernandez Garcia C, Muro M, Minguela Puras A, Moreno-Docon A, Torres-Cantero AM, Munoz Garcia M, Serrano M, Iacobelli M, Carlo-Stella C, Wei LJ, Richardson PG, Moraleda JM. Phase IIB, Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Intravenous Defibrotide for the Prevention and Treatment of Respiratory Distress and Cytokine Release Syndrome in COVID-19. Eur J Haematol. 2026 May 12. doi: 10.1111/ejh.70214. Online ahead of print.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Defibrotide in people with COVID19, run by Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia at 6 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical improvement. (time frame: 7,15, 30 day). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04348383, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jun 2023.