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Defibrotide in COVID-19 Pneumonia (DEFI-VID19)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04335201
Recruitment Status : Not yet recruiting
First Posted : April 6, 2020
Last Update Posted : April 6, 2020
Sponsor:
Information provided by (Responsible Party):
Ciceri Fabio, IRCCS San Raffaele

Brief Summary:

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


Condition or disease Intervention/treatment Phase
Patients With COVID-19 Pneumonia Will Allow to Detect an Absolute Reduction in the Rate of Respiratory-failure Drug: Defibrotide Injection Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: 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 institutional observational study (ClinicalTrials.gov Identifier: NCT04318366)
Masking: None (Open Label)
Masking Description: Italian Hospital
Primary Purpose: Treatment
Official Title: Use of Defibrotide to Reduce Progression of Acute Respiratory Failure Rate in Patients With COVID-19 Pneumonia
Estimated Study Start Date : April 6, 2020
Estimated Primary Completion Date : September 30, 2020
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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




Primary Outcome Measures :
  1. to able to reduce the progression of acute respiratory failure [ Time Frame: 14 days ]

    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:

    1. severe gas transfer deficit (PaO2/FiO2 < 200);
    2. persistent respiratory distress while receiving oxygen (persistent marked dyspnea, use of accessory respiratory muscles, paradoxical respiratory movements);
    3. transfer to the intensive care unit;
    4. 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.


Secondary Outcome Measures :
  1. Adverse events [ Time Frame: 7 days ]
    To evaluate the safety of Defibrotide will be analyzed the frequency and incidence of Treatment-Related Adverse Events as Assessed by CTCAE v4.0

  2. duration of hospitalization [ Time Frame: 14 days ]
    evaluate the time of hospitalization that will determine how much and how the administration of defibrotide can resolve the infection

  3. systemic inflammation [ Time Frame: 14 days ]

    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.


  4. overall survival [ Time Frame: 28 days ]
    To evaluate the overall survival at day+28 after start treatment with Defibrotide



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04335201


Contacts
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Contact: Fabio Ciceri, MD +39 02 2643 ext 7503 ciceri.clinicaltrials@hsr.it
Contact: Stefania Trinca +39 02 2643 ext 4289 defi-vid19@hsr.it ; trinca.stefania@hsr.it

Sponsors and Collaborators
IRCCS San Raffaele
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Responsible Party: Ciceri Fabio, Prof., Director Clinical Trial Unit, IRCCS San Raffaele
ClinicalTrials.gov Identifier: NCT04335201    
Other Study ID Numbers: DEFI-VID19
First Posted: April 6, 2020    Key Record Dates
Last Update Posted: April 6, 2020
Last Verified: April 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ciceri Fabio, IRCCS San Raffaele:
COVID-19
respiratory failure
Defibrotide
mechanical ventilation
Additional relevant MeSH terms:
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Pneumonia
Respiratory Insufficiency
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Respiration Disorders
Defibrotide
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors