Use of Defibrotide to Reduce Progression of Acute Respiratory Failure Rate in Patients With COVID-19 Pneumonia
Latest Information Update: 26 Aug 2022
At a glance
- Drugs Defibrotide (Primary)
- Indications Adult respiratory distress syndrome; COVID-19 pneumonia
- Focus Therapeutic Use
- Acronyms DEFI-VID19
- 18 Jul 2022 Status changed from active, no longer recruiting to completed.
- 04 Feb 2022 Status changed from recruiting to active, no longer recruiting.
- 04 Feb 2022 Planned End Date changed from 31 Aug 2021 to 1 Mar 2022.
Most Recent Events
Trial Overview
Purpose
Phase II, prospective, interventional, single-arm, multicentric, open label trial, with a parallel retrospective collection of data on not treated patients from IRCCS, San Raffaele Scientific Institute included in the institutional observational study. A sample of 50 patients with COVID-19 pneumonia will allow to detect an absolute reduction in the rate of Respiratory-failure at day+14 after treatment of 20%, assuming that the actual rate of failure in the corresponding not treated patients is 70% (alpha=5%, power=90%, two-sided test). The software PASS15 was used for calculations. The study will also include a parallel retrospective group of temporally concomitant patients from IRCCS, San Raffaele Scientific Institute, who did not receive an experimental treatment and who are enrolled in an already IRB approved observational study
Primary Endpoints
to able to reduce the progression of acute respiratory failure
description: To demonstrate that the treatment with Defibrotide administered intravenously in addition to the best available therapy according to institutional guidelines (protease inhibitors antiviral treatment and hydroxychloroquine (HCQ), and if needed, metilprednisolone is able to reduce the progression of acute respiratory failure, the need of mechanical ventilation, the transfer to the intensive care unit or death, in patients with severe COVID-19 pneumonia.
Patients with a baseline PaO2/FiO2 ≥ 200: progression of respiratory failure is defined by:
severe gas transfer deficit (PaO2/FiO2 < 200);
persistent respiratory distress while receiving oxygen (persistent marked dyspnea, use of accessory respiratory muscles, paradoxical respiratory movements);
transfer to the intensive care unit;
death. The rate will be calculated as the proportion of patients who experienced at least one of the events above by day+14 from treatment start.
time_frame: 14 days
Other Endpoints
Adverse events
description: To evaluate the safety of Defibrotide will be analyzed the frequency and incidence of Treatment-Related Adverse Events as Assessed by CTCAE v4.0
time_frame: 7 days
duration of hospitalization
description: evaluate the time of hospitalization that will determine how much and how the administration of defibrotide can resolve the infection
time_frame: 14 days
systemic inflammation
description: To evaluate the level of PCR, LDH, ferritin, IL-10, IL-6, TNF-alpha, IFN-gamma, PTX3 at day +7 and +14 after start of treatment with Defibrotide.
performed per day. Laboratory values performed at day 7 and 14 will be analyzed and compared with each other to understand their progress.
time_frame: 14 days
overall survival
description: To evaluate the overall survival at day+28 after start treatment with Defibrotide
time_frame: 28 days [1]
Diseases Treated
| Indication | Qualifiers | Patient Segments |
|---|---|---|
| Adult respiratory distress syndrome | treatment | - |
| COVID-19 pneumonia | treatment | severe |
Biomarker
| NCT Number | Biomarker Name | Biomarker Function |
|---|---|---|
| NCT04335201 | Ferritin | Outcome Measure |
| Interferon Gamma (IFNg) | Outcome Measure | |
| Interleukin-10 (IL-10) | Outcome Measure | |
| Interleukin-6 (IL-6) | Outcome Measure | |
| neuropeptide S | Eligibility Criteria | |
| PTX3 | Outcome Measure | |
| Tumor necrosis factor alpha (TNF-alpha) | Outcome Measure |
Subjects
- Subject Type patients
-
Number
Planned: 50
Actual: 50
- Sex male & female
- Age Group 53-71 (median 61) years; adult; elderly
Patient Inclusion Criteria
- Documented COVID-19 pneumonia: defined as upper respiratory tract specimen (nasopharyngeal swab (NPS) or viral throat swab) positive for COVID-19 and/or imaging at computed tomography scan suggestive of COVID-19 pneumonia - Oxygen saturation (SaO2) of 92% or less without oxygen support, or reduction of 3% from basal value of SaO2, or a ratio of the partial pressure of oxygen (PaO2) to the fraction of inspired oxygen (FiO2) (PaO2/FiO2) below 300. - Any gender - Age ≥ 18 years - Written informed consent or as per Ethical Committee indication in case of patients not able to express written informed consent
Patient Exclusion Criteria
- Onset of COVID-19 pneumonia >14 days - Orotracheal intubation - Uncontrolled systemic infection (other than COVID-19) - Concomitant use of thrombolytic therapy Concomitant systemic anticoagulant therapy (e.g. heparin, warfarin, direct thrombin inhibitors and direct factor Xa inhibitors) - Haemodynamic instability, defined as inability to maintain mean arterial pressure with single pressor support - Hypersensitivity to the active substance or to any of the excipients of the experimental drug - Patients who, based on the investigator's clinical judgement, are not able to receive the treatment - Pregnancy or breastfeeding patient
Trial Details
Identifiers
| Identifier | Owner |
|---|---|
| NCT04335201 | ClinicalTrials.gov: US National Institutes of Health |
| EudraCT2020-001513-20 | European Clinical Trials Database |
| DEFI-VID19 | - |
Trial Dates
-
Initiation Dates
Planned : 06 Apr 2020
Actual : 06 May 2020
-
Primary Completion Dates
Planned : 20 Jun 2021
Actual : 07 Apr 2021
-
End Dates
Planned : 01 Mar 2022
Actual : 28 May 2021
Other Details
- Design multicentre; open; parallel; prospective; retrospective
- Phase of Trial Phase II
- Location Italy
- Focus Therapeutic Use
Interventions
| Drugs | Route | Formulation |
|---|---|---|
| DefibrotidePrimary Drug | Intravenous | Infusion, Injection |
Arm Label
with the experimental drug: Defibrotide 25 mg/kg body weight total dose in 2 hours duration infusion each, every 6 hours (Defibrotide 6.25 mg/kg body weight each dose) Treatment duration = 7 days
Drug: Defibrotide Injection (Patients will be treated according to the standard institutional procedures and will receive the best available treatment as per institutional guidelines in association with the experimental drug: Defibrotide 25 mg/kg body weight total dose in 2 hours duration infusion each, every 6 hours (Defibrotide 6.25 mg/kg body weight each dose) Treatment duration = 7 days)
Results
Publications
-
Ruggeri A, Voza A, Liberatore C, Catalano G, Corrado F, Di Filippo L, et al. Use of Defibrotide in Patients with COVID-19 Pneumonia; Results of the Defi-VID19 Phase 2 Trial. ASH-Hem-2021 2021; abstr. 672.
Available from: URL: https://ash.confex.com/ash/2021/webprogram/Paper147784.html
Trial Centres
Investigators
| Investigator | Centre Name | Trial Centre Country |
|---|---|---|
|
Fabio Ciceri, MD
+39 02 2643 Ext: 7503
show details
ciceri.clinicaltrials@hsr.it |
-
|
|
|
Stefania Trinca
+39 02 2643 Ext: 4289
show details
defi-vid19@hsr.it ; trinca.stefania@hsr.it |
-
|
Trial History
| Event Date | Event Type | Comment |
|---|---|---|
| 26 Aug 2022 | Other trial event | Last checked against European Clinical Trials Database record. Updated 26 Aug 2022 |
| 22 Jul 2022 | Other trial event | Last checked against ClinicalTrials.gov: US National Institutes of Health record. Updated 22 Jul 2022 |
| 18 Jul 2022 | Status change - completed | Status changed from active, no longer recruiting to completed. Updated 22 Jul 2022 |
| 04 Feb 2022 | Status change - active, no longer recruiting | Status changed from recruiting to active, no longer recruiting. Updated 10 Feb 2022 |
| 04 Feb 2022 | Completion date | Planned End Date changed from 31 Aug 2021 to 1 Mar 2022. Updated 09 Feb 2022 |
| 14 Dec 2021 | Results | Results presented at the 63rd American Society of Hematology Annual Meeting and Exposition Updated 31 Jan 2022 |
| 16 Feb 2021 | Biomarker Update | Biomarkers information updated Updated 04 Nov 2021 |
| 12 Feb 2021 | Completion date | Planned End Date changed from 31 Dec 2020 to 31 Aug 2021. Updated 19 Feb 2021 |
| 12 Feb 2021 | Other trial event | Planned primary completion date changed from 30 Sep 2020 to 20 Jun 2021. Updated 19 Feb 2021 |
| 26 Jun 2020 | Status change - recruiting | Status changed from not yet recruiting to recruiting. Updated 26 Jun 2020 |
| 26 Jun 2020 | Other trial event | New source identified and integrated European Clinical Trials Database (EudraCT2020-001513-20). Updated 26 Jun 2020 |
| 07 Apr 2020 | New trial record | New trial record Updated 07 Apr 2020 |
References
-
ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2023;.
Available from: URL: http://clinicaltrials.gov -
European Clinical Trials Database. Trial-Reg 2023;.
Available from: URL: https://www.clinicaltrialsregister.eu -
Ruggeri A, Voza A, Liberatore C, Catalano G, Corrado F, Di Filippo L, et al. Use of Defibrotide in Patients with COVID-19 Pneumonia; Results of the Defi-VID19 Phase 2 Trial. ASH-Hem-2021 2021; abstr. 672.
Available from: URL: https://ash.confex.com/ash/2021/webprogram/Paper147784.html
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