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A Single-Arm Safety and Feasibility Study of Defibrotide for the Treatment of Severe COVID-19 (DF in COVID19)

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ClinicalTrials.gov Identifier: NCT04652115
Recruitment Status : Not yet recruiting
First Posted : December 3, 2020
Last Update Posted : December 3, 2020
Sponsor:
Collaborator:
Jazz Pharmaceuticals
Information provided by (Responsible Party):
Paul G. Richardson, M.D., Brigham and Women's Hospital

Brief Summary:
The goal of this study is to evaluate the safety and feasibility of defibrotide in COVID-19 pneumonia.

Condition or disease Intervention/treatment Phase
Covid19 Drug: Defibrotide Phase 2

Detailed Description:

This study is a prospective, single-arm, two-cohort, phase 2 pilot study that will evaluate the safety and efficacy of defibrotide in clinically severe COVID-19. The defibrotide dose that is approved by the FDA for the treatment of post-HSCT VOD/SOS (6.25 mg/kg IV q6 hours) will be used.

Cohort 1 will consist of patients with COVID-19 pneumonia confirmed by PCR and radiography, who are hospitalized with an oxygen requirement (either supplemental O2 or mechanical ventilation), are not on therapeutic dose anticoagulation, and require no more than one vasopressive agent to maintain hemodynamic stability. Cohort 2 will consist of patients with COVID-19 pneumonia confirmed by PCR and radiography, who are hospitalized in the ICU and are at elevated risk of hemorrhage and/or hypotension, the former defined as a requirement for therapeutic dose anticoagulation for active thrombosis, ECMO, or CRRT, and the latter defined as a requirement for two vasopressive agents to maintain hemodynamic stability.

In cohort 2 only, a 6+6 dose de-escalation design will be utilized, in which if 2 of 6 DLTs are experienced in the first 6 subjects, the dose will be reduced from 6.25 mg/kg IV q6hrs to 10mg/kg/d CIVI. If there are 0 or 1 DLTs in the first 6 subjects at the FDA-approved dose, another 6 subjects will be enrolled at the same dose. Grade 3/4 hemorrhage and significant new hypotension will be considered DLT's.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Prospective, single arm, two cohort clinical trial.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single-Arm Safety and Feasibility Study of Defibrotide for the Treatment of Severe COVID-19
Estimated Study Start Date : January 1, 2021
Estimated Primary Completion Date : November 1, 2022
Estimated Study Completion Date : November 1, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Defibrotide
Defibrotide IV
Drug: Defibrotide
Deibrotide via IV




Primary Outcome Measures :
  1. The rate of adverse event of special interest (bleeding and hypotension) [ Time Frame: Up to 21 days ]
    The rate of adverse event of special interest (bleeding and hypotension)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Age ≥18 years.
  2. Active COVID-19 infection confirmed by positive SARS-CoV-2 PCR.
  3. Radiographic evidence of bilateral pulmonary infiltrates.
  4. A life expectancy of at least 24 hours.
  5. Score of 4-7 on the WHO ordinal scale.
  6. Prophylactic dose anticoagulation is allowed for enrollment into cohort 1. Therapeutic dose anticoagulation for active thrombosis, ECMO, and/or continuous renal replacement therapy (CRRT) is allowed for enrollment into cohort 2 if there is no evidence of bleeding after at least 24 hours of anticoagulation.
  7. Patient or surrogate able to provide informed consent

Exclusion Criteria:

  1. Clinically significant acute bleeding.
  2. Concomitant use of thrombolytic therapy (e.g. t-PA).
  3. Hemodynamic instability, defined as a requirement for >1 vasopressor agent for enrollment into cohort 1, and a requirement for >2 vasopressor agents for enrollment into cohort 2
  4. Known allergy or hypersensitivity to DF.
  5. Pregnant or lactating.

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): NCT04652115


Locations
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United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02214
Contact: Paul G Richardson, MD       Paul_Richardson@dfci.harvard.edu   
Principal Investigator: Paul G Richardson, MD         
Sponsors and Collaborators
Brigham and Women's Hospital
Jazz Pharmaceuticals
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Responsible Party: Paul G. Richardson, M.D., Principal Investigator, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT04652115    
Other Study ID Numbers: 2020P003203
First Posted: December 3, 2020    Key Record Dates
Last Update Posted: December 3, 2020
Last Verified: December 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Defibrotide
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors