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Use of Defibrotide to Reduce Progression of Acute Respiratory Failure Rate in Patients With COVID-19 Pneumonia

Trial Profile

Use of Defibrotide to Reduce Progression of Acute Respiratory Failure Rate in Patients With COVID-19 Pneumonia

Status: Recruiting
Phase of Trial: Phase II

Latest Information Update: 26 Jun 2020

At a glance

  • Drugs Defibrotide (Primary)
  • Indications COVID 2019 infections; Pneumonia
  • Focus Therapeutic Use
  • Acronyms DEFI-VID19
  • Most Recent Events

    • 26 Jun 2020 Status changed from not yet recruiting to recruiting.
    • 07 Apr 2020 New trial record

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
COVID 2019 infections treatment -
Pneumonia treatment severe

Subjects

  • Subject Type patients
  • Number

    Planned: 50

  • Sex male & female
  • Age Group ≥ 18 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 : 30 Sep 2020

  • End Dates

    Planned : 31 Dec 2020

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)

Trial Centres

Investigators

Investigator Centre Name Trial Centre Country
Fabio Ciceri, MD
+39 02 2643 Ext: 7503
ciceri.clinicaltrials@hsr.it
show details
-
Stefania Trinca
+39 02 2643 Ext: 4289
defi-vid19@hsr.it ; trinca.stefania@hsr.it
show details
-

Centres

Centre Name Location Trial Centre Country
-
-
-
IRCCS San Raffaele
-
-

Trial History

Event Date Event Type Comment
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

  1. ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2016;.

    Available from: URL: http://clinicaltrials.gov
  2. European Clinical Trials Database. Trial-Reg 2016;.

    Available from: URL: https://www.clinicaltrialsregister.eu
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