The goal of this study is to evaluate the safety and feasibility of defibrotide in COVID-19 pneumonia.
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.
Drug: Defibrotide
Deibrotide via IV
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.
Brigham and Women's Hospital
Boston, Massachusetts, United States
Investigator: Paul G Richardson, MD
Contact: 617-632-2127
Paul_Richardson@dfci.harvard.edu
Investigator: Paul G Richardson, MD
Not Provided