Defibrotide for the Treatment of Severe COVID-19

A Single-Arm Safety and Feasibility Study of Defibrotide for the Treatment of Severe COVID-19

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

Study Overview

• Status: Recruiting
• Conditions: Covid19
• Intervention / Treatment: Drug: Defibrotide

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.

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02214
      • Recruiting
      • Brigham and Women's Hospital
      • Contact: Paul G Richardson, MD; Phone Number: 617-632-2127; Email: Paul_Richardson@dfci.harvard.edu
      • Principal Investigator: Paul G Richardson, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Defibrotide; Defibrotide IV	Drug: Defibrotide; Deibrotide via IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of adverse event of special interest (bleeding and hypotension)	The rate of adverse event of special interest (bleeding and hypotension)	Up to 21 days

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: Jazz Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: December 1, 2020
• First Submitted That Met QC Criteria: December 2, 2020
• First Posted (Actual): December 3, 2020

Study Record Updates

• Last Update Posted (Actual): May 26, 2026
• Last Update Submitted That Met QC Criteria: May 22, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; defibrotide
• Other Study ID Numbers: 2020P003203

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No