Defibrotide for the Treatment of Severe COVID-19

Sponsor
Brigham and Women's Hospital (Other)
Overall Status
Recruiting
CT.gov ID
NCT04652115
Collaborator
Jazz Pharmaceuticals (Industry)
42
1
1
34
1.2

Study Details

Study Description

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
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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
42 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Intervention Model Description:
Prospective, single arm, two cohort clinical trial.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
Actual Study Start Date :
Jan 1, 2021
Anticipated Primary Completion Date :
Nov 1, 2022
Anticipated Study Completion Date :
Nov 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Defibrotide

Defibrotide IV

Drug: Defibrotide
Deibrotide via IV

Outcome Measures

Primary Outcome Measures

  1. The rate of adverse event of special interest (bleeding and hypotension) [Up to 21 days]

    The rate of adverse event of special interest (bleeding and hypotension)

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 100 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Brigham and Women's Hospital Boston Massachusetts United States 02214

Sponsors and Collaborators

  • Brigham and Women's Hospital
  • Jazz Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
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:
Dec 3, 2020
Last Update Posted:
Jul 29, 2021
Last Verified:
Jul 1, 2021
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jul 29, 2021