COVIDPhase 1NCT04530604
Defibrotide Therapy for SARS-CoV2 (COVID-19) Acute Respiratory Distress Syndrome (ARDS)
A Phase 1 study testing Defibrotide in people with COVID and Sars-CoV2, run by Gregory Yanik at 1 site in United States.
Trial summary
This clinical trial will enroll participants that have pneumonia caused by the COVID-19 virus. During the study patients will receive 7 to up to 14 days of defibrotide. After completing the treatment, participants will have 30 day follow-up check-up to assess for adverse events and clinical status. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- What is being tested?
- Defibrotide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2020to 9 Apr 2021
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Presence of SARS-CoV2 infection, confirmed by real-time reverse transcription polymerase chain reaction (RT-PCR) assay from a nasopharyngeal swab specimen or other diagnostic test for SARS-CoV2.
- Serum D-Dimer ≥ 2.0 mcg/ml.
- Patients with Acute Respiratory Distress Syndrome (ARDS) as determined by the following criteria (Berlin criteria adaptation):
- Radiographic evidence of bilateral lung disease (opacities or ground glass opacification) on chest radiograph (CXR) or computed tomography (CT), and the opacities not fully explained by pleural effusions, cardiac failure or fluid overload.
- Impairment of oxygenation, as defined by the ratio of arterial oxygen tension to fraction of inspired oxygen (PaO2/FiO2) ≤ 300 mmHg (millimeters of mercury).
- Patients must provide voluntary written informed consent to be eligible for study. For patients who are medically unable to provide consent, their designated proxy or legal guardian will provide informed consent. The consenting process is described in Appendix II.
- Patients actively participating in another clinical trial for the management of SARS-CoV2 are eligible provided those trials do not directly involve an anti-platelet, anti-coagulant or anti-fibrinolytic agent. (Patients enrolled on investigational trials utilizing anti-viral specific agents, cytokine inhibitors, tyrosine kinase inhibitors, or other anti-inflammatory agents are still eligible).
Who cannot join
- Concomitant use of heparin, systemic anticoagulants, and/or fibrinolytics are not permitted within 12 hours, with the exception of heparin flushes for centrally placed catheters, fibrinolytic instillation for central venous line occlusion, or in the in-flow circuit for patients on continuous veno-venous hemodialysis.
- Clinically significant acute bleeding, including (but not limited to one of the following): pulmonary hemorrhage (diffuse alveolar hemorrhage), intracranial bleed, gastro-intestinal hemorrhage (gross hematemesis or hematochezia), gross hematuria or uncontrolled epistaxis irrespective of the amount of blood loss, within the prior 3 days.
- On mechanical ventilation for > 96 consecutive hours.
- Serum platelet count < 50,000/Microliters (uL). Transfusion of platelets to achieve a level > 50,000/uL is not allowed for eligibility.
- Serum fibrinogen < 150 mg/dl. Transfusion of fresh frozen plasma or cryoprecipitate to achieve a level > 150 mg/dl is not allowed for eligibility.
- Positive blood culture for a bacterial pathogen within the prior 24 hours prior to study entry, and/or the presence of bacterial pneumonia.
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- Hemodynamic instability as defined by a requirement for 2 or more vasopressors (not including renal-doses of dopamine).
- Concurrent use of Extracorporeal membrane oxygenation (ECMO).
- Patients with a previously known hypersensitivity reaction to defibrotide, or any of its excipients.
- Females who are pregnant or breastfeeding.
- History of cerebrovascular accident (i.e. thrombotic or hemorrhagic stroke) within 3 months prior to study entry.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Defibrotide Therapy for SARS-CoV2 Acute Respiratory Distress Syndrome (ARDS)
This clinical trial will enroll participants that have pneumonia caused by the COVID-19 virus. During the study patients will receive 7 to up to 14 days of defibrotide. After completing the treatment, participants will have 30 day follow-up check-up to assess for adverse events and clinical status. This final assessment can be done virtually, by telephone or electronically (email) if the patient cannot be contacted by phone. No in-person visit is required.
The hypothesis of this trial is that defibrotide therapy given to patients with severe SARS-CoV2 ARDS will be safe and associated with improved overall survival, within 28 days of therapy initiation.
- Conditions
- COVID, Sars-CoV2, COVID-19, Acute Respiratory Distress Syndrome
- Being tested
- Defibrotide
- Medical subject headings
- COVID-19, Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DefibrotideDrug
Also called defitelio
All patients will receive 25 milligram/kilogram/day (mg/kg/day) of defibrotide, given in 4 divided doses (approximately every 6 hours), each dose infused over 2-hours intravenously (IV).
The planned duration of study therapy is 7 days (while in the hospital), with the following qualifications:
- Patients who respond to study therapy prior to day 7 (able to discontinue oxygen) will discontinue study therapy at that earlier time point.
- Patients who have not responded to study therapy by day 7 of therapy, evidenced by <20% reduction (or a worsening) of the amount of supplemental oxygen they are receiving, will discontinue study therapy at day 7.
- Patients who have evidence of a partial pulmonary response by day 7 (>20% reduction in supplemental oxygen requirement, but still require supplemental oxygen) may elect to continue to receive study drug through an additional 7 days of study (total 14-day therapy course).
| Study group | Role | What they receive |
|---|---|---|
| Defibrotide | Experimental | Not described Receives: Drug: Defibrotide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Major Hemorrhagic Complications Within 14 Days of Initiation of Treatment
Major hemorrhagic complications will be based on the International Society on Thrombosis and Haemostasis Bleeding scale.
- Fatal Bleeding, and/or
- Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular, pericardial, or intramuscular with compartment syndrome, and/or
- Bleeding associated with a decline in hemoglobin level of > 2.0 g/dl, leading to transfusion of two or more units of whole blood or red cells.
- In addition, symptomatic alveolar hemorrhage, macroscopic hematuria, uncontrolled menorrhagia or epistaxis or bleeding from any wound site would also be considered a major hemorrhagic event.
Measured: 14 days
Secondary outcomes (6)
Overall Survival
Number of patients who are alive at Day 28 after starting treatment.
Measured: 28 days
Overall Survival
Number of patients who are alive at Day 14 after starting treatment.
Measured: 14 days
Ventilator-free Survival
Day 14 ventilator-free survival will be summarized by the number of patients who are both alive and not using a ventilator at Day 14 after starting treatment.
Measured: 14 days
Number of Ventilator Free Days Within 14 Days of Study Entry
Measured: 14 days
The Time to Improvement in Oxygenation
Improvement in oxygenation defined as an increase in ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) of 50 (or greater) compared to the nadir of PaO2/FiO2.
Measured: up to 14 days
Mean Change in the WHO COVID-19 Ordinal Scale During Therapy
Ordinal scale:
- = Ambulatory, no limitation of activities;
- = Ambulatory, Activity LImited;
- = Hospitalized, no oxygen therapy;
- = Oxygen by mask or nasal cannula;
- = Non-invasive ventilation or high-flow oxygen (O2);
- = Intubation/mechanical ventilation;
- = Intubation/Mechanical ventilation plus one of the following: Pressors, Extracorporeal membrane oxygenation (ECMO) or Dialysis;
- = Decased/Death Key: For change in ordinal score, negative values represent a decline in WHO score from baseline to day 14 (improvement of condition); positive values represent an increase (worsening of condition).
Measured: up to 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2020
- Study start1 Oct 2020
- Primary completion26 Mar 2021
- Study completion9 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for COVIDStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gregory Yanik
- Sponsor type
- University, hospital or other
- Collaborators
- Jazz Pharmaceuticals
- Responsible party
- Sponsor-investigator, Gregory Yanik, University of Michigan
- Investigators
- Gregory Yanik, MD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04530604
- Sponsor's protocol ID
- HUM00182089
- Status last verified
- Jun 2022
- First submitted
- 25 Aug 2020
- Last updated
- 9 May 2023
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Frame D, Scappaticci GB, Braun TM, Maliarik M, Sisson TH, Pipe SW, Lawrence DA, Richardson PG, Holinstat M, Hyzy RC, Kaul DR, Gregg KS, Lama VN, Yanik GA. Defibrotide Therapy for SARS-CoV-2 ARDS. Chest. 2022 Aug;162(2):346-355. doi: 10.1016/j.chest.2022.03.046. Epub 2022 Apr 9.
PubMed 35413279
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Defibrotide Therapy for SARS-CoV2 Acute Respiratory Distress Syndrome (ARDS)
- ClinicalTrials.gov ID
- NCT04530604
- Acronym / sponsor ID
- HUM00182089
- Conditions
- COVID, Sars-CoV2, COVID-19, Acute Respiratory Distress Syndrome
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Gregory YanikUniversity, hospital or other
- Collaborators
- Jazz Pharmaceuticals
- Study start
- 1 Oct 2020 (actual)
- Primary completion
- 26 Mar 2021 (actual)
- Study completion
- 9 Apr 2021 (actual)
- First posted
- 28 Aug 2020 (actual)
- Results
- Posted 9 May 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This clinical trial will enroll participants that have pneumonia caused by the COVID-19 virus. During the study patients will receive 7 to up to 14 days of defibrotide. After completing the treatment, participants will have 30 day follow-up check-up to assess for adverse events and clinical status. This final assessment can be done virtually, by telephone or electronically (email) if the patient cannot be contacted by phone. No in-person visit is required.
The hypothesis of this trial is that defibrotide therapy given to patients with severe SARS-CoV2 ARDS will be safe and associated with improved overall survival, within 28 days of therapy initiation.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Defibrotide | Experimental | Drug: Defibrotide |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Presence of SARS-CoV2 infection, confirmed by real-time reverse transcription polymerase chain reaction (RT-PCR) assay from a nasopharyngeal swab specimen or other diagnostic test for SARS-CoV2.
- Serum D-Dimer ≥ 2.0 mcg/ml.
- Patients with Acute Respiratory Distress Syndrome (ARDS) as determined by the following criteria (Berlin criteria adaptation):
- Patients must provide voluntary written informed consent to be eligible for study. For patients who are medically unable to provide consent, their designated proxy or legal guardian will provide informed consent. The consenting process is described in Appendix II.
- Patients actively participating in another clinical trial for the management of SARS-CoV2 are eligible provided those trials do not directly involve an anti-platelet, anti-coagulant or anti-fibrinolytic agent. (Patients enrolled on investigational trials utilizing anti-viral specific agents, cytokine inhibitors, tyrosine kinase inhibitors, or other anti-inflammatory agents are still eligible).
Key exclusion criteria (11 listed)
- Concomitant use of heparin, systemic anticoagulants, and/or fibrinolytics are not permitted within 12 hours, with the exception of heparin flushes for centrally placed catheters, fibrinolytic instillation for central venous line occlusion, or in the in-flow circuit for patients on continuous veno-venous hemodialysis.
- Clinically significant acute bleeding, including (but not limited to one of the following): pulmonary hemorrhage (diffuse alveolar hemorrhage), intracranial bleed, gastro-intestinal hemorrhage (gross hematemesis or hematochezia), gross hematuria or uncontrolled epistaxis irrespective of the amount of blood loss, within the prior 3 days.
- On mechanical ventilation for > 96 consecutive hours.
- Serum platelet count < 50,000/Microliters (uL). Transfusion of platelets to achieve a level > 50,000/uL is not allowed for eligibility.
- Serum fibrinogen < 150 mg/dl. Transfusion of fresh frozen plasma or cryoprecipitate to achieve a level > 150 mg/dl is not allowed for eligibility.
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 |
|---|---|---|
| DefibrotideAlso: defitelioAll patients will receive 25 milligram/kilogram/day (mg/kg/day) of defibrotide, given in 4 divided doses (approximately every 6 hours), each dose infused over 2-hours intravenously (IV). The planned duration of study therapy is 7 days (while in the hospital), with the following qualifications: * Patients who respond to study therapy prior to day 7 (able to discontinue oxygen) will discontinue study therapy at that earlier time point. * Patients who have not responded to study therapy by day 7 of therapy, evidenced by <20% reduction (or a worsening) of the amount of supplemental oxygen they are receiving, will discontinue study therapy at day 7. * Patients who have evidence of a partial pulmonary response by day 7 (>20% reduction in supplemental oxygen requirement, but still require supplemental oxygen) may elect to continue to receive study drug through an additional 7 days of study (total 14-day therapy course). | Drug | Defibrotide |
Primary outcome
Number of Major Hemorrhagic Complications Within 14 Days of Initiation of Treatment
Time frame: 14 days
Major hemorrhagic complications will be based on the International Society on Thrombosis and Haemostasis Bleeding scale. 1. Fatal Bleeding, and/or 2. Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular, pericardial, or intramuscular with compartment syndrome, and/or 3. Bleeding associated with a decline in hemoglobin level of > 2.0 g/dl, leading to transfusion of two or more units of whole blood or red cells. 4. In addition, symptomatic alveolar hemorrhage, macroscopic hematuria, uncontrolled menorrhagia or epistaxis or bleeding from any wound site would also be considered a major hemorrhagic event.
6 secondary outcomes
Overall Survival
Time frame: 28 days
Overall Survival
Time frame: 14 days
Ventilator-free Survival
Time frame: 14 days
Number of Ventilator Free Days Within 14 Days of Study Entry
Time frame: 14 days
The Time to Improvement in Oxygenation
Time frame: up to 14 days
Mean Change in the WHO COVID-19 Ordinal Scale During Therapy
Time frame: up to 14 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35413279Frame D, Scappaticci GB, Braun TM, Maliarik M, Sisson TH, Pipe SW, Lawrence DA, Richardson PG, Holinstat M, Hyzy RC, Kaul DR, Gregg KS, Lama VN, Yanik GA. Defibrotide Therapy for SARS-CoV-2 ARDS. Chest. 2022 Aug;162(2):346-355. doi: 10.1016/j.chest.2022.03.046. Epub 2022 Apr 9.
- 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.
Gregory Yanik, MD principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Defibrotide in people with COVID and Sars-CoV2, run by Gregory Yanik at 1 site in United States.
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 11 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 9 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Major Hemorrhagic Complications Within 14 Days of Initiation of Treatment (time frame: 14 days). 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 NCT04530604, 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 9 May 2023.