Defibrotide Therapy for SARS-CoV2 (COVID-19) Acute Respiratory Distress Syndrome (ARDS)

NCT ID: NCT04530604

Last Updated: 2023-05-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-01
• Study Completion Date: 2021-04-09

Brief Summary

This clinical trial will enroll participants that have pneumonia caused by the COVID-19 virus. During the study patients will receive 7 to up to 14 days of defibrotide. After completing the treatment, participants will have 30 day follow-up check-up to assess for adverse events and clinical status. This final assessment can be done virtually, by telephone or electronically (email) if the patient cannot be contacted by phone. No in-person visit is required.

The hypothesis of this trial is that defibrotide therapy given to patients with severe SARS-CoV2 ARDS will be safe and associated with improved overall survival, within 28 days of therapy initiation.

Conditions

COVID; Sars-CoV2; COVID-19; Acute Respiratory Distress Syndrome

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Defibrotide

Group Type: EXPERIMENTAL

Defibrotide

Intervention Type: DRUG

All patients will receive 25 milligram/kilogram/day (mg/kg/day) of defibrotide, given in 4 divided doses (approximately every 6 hours), each dose infused over 2-hours intravenously (IV).

The planned duration of study therapy is 7 days (while in the hospital), with the following qualifications:

• Patients who respond to study therapy prior to day 7 (able to discontinue oxygen) will discontinue study therapy at that earlier time point.
• Patients who have not responded to study therapy by day 7 of therapy, evidenced by <20% reduction (or a worsening) of the amount of supplemental oxygen they are receiving, will discontinue study therapy at day 7.
• Patients who have evidence of a partial pulmonary response by day 7 (>20% reduction in supplemental oxygen requirement, but still require supplemental oxygen) may elect to continue to receive study drug through an additional 7 days of study (total 14-day therapy course).

Interventions

Defibrotide

All patients will receive 25 milligram/kilogram/day (mg/kg/day) of defibrotide, given in 4 divided doses (approximately every 6 hours), each dose infused over 2-hours intravenously (IV).

The planned duration of study therapy is 7 days (while in the hospital), with the following qualifications:

• Patients who respond to study therapy prior to day 7 (able to discontinue oxygen) will discontinue study therapy at that earlier time point.
• Patients who have not responded to study therapy by day 7 of therapy, evidenced by <20% reduction (or a worsening) of the amount of supplemental oxygen they are receiving, will discontinue study therapy at day 7.
• Patients who have evidence of a partial pulmonary response by day 7 (>20% reduction in supplemental oxygen requirement, but still require supplemental oxygen) may elect to continue to receive study drug through an additional 7 days of study (total 14-day therapy course).

Intervention Type: DRUG

Other Intervention Names

defitelio

Eligibility Criteria

Inclusion Criteria

• Presence of SARS-CoV2 infection, confirmed by real-time reverse transcription polymerase chain reaction (RT-PCR) assay from a nasopharyngeal swab specimen or other diagnostic test for SARS-CoV2.
• Serum D-Dimer ≥ 2.0 mcg/ml.
• Patients with Acute Respiratory Distress Syndrome (ARDS) as determined by the following criteria (Berlin criteria adaptation):

• Radiographic evidence of bilateral lung disease (opacities or ground glass opacification) on chest radiograph (CXR) or computed tomography (CT), and the opacities not fully explained by pleural effusions, cardiac failure or fluid overload.
• Impairment of oxygenation, as defined by the ratio of arterial oxygen tension to fraction of inspired oxygen (PaO2/FiO2) ≤ 300 mmHg (millimeters of mercury).
• Patients must provide voluntary written informed consent to be eligible for study. For patients who are medically unable to provide consent, their designated proxy or legal guardian will provide informed consent. The consenting process is described in Appendix II.
• Patients actively participating in another clinical trial for the management of SARS-CoV2 are eligible provided those trials do not directly involve an anti-platelet, anti-coagulant or anti-fibrinolytic agent. (Patients enrolled on investigational trials utilizing anti-viral specific agents, cytokine inhibitors, tyrosine kinase inhibitors, or other anti-inflammatory agents are still eligible).

Exclusion Criteria

• Concomitant use of heparin, systemic anticoagulants, and/or fibrinolytics are not permitted within 12 hours, with the exception of heparin flushes for centrally placed catheters, fibrinolytic instillation for central venous line occlusion, or in the in-flow circuit for patients on continuous veno-venous hemodialysis.
• Clinically significant acute bleeding, including (but not limited to one of the following): pulmonary hemorrhage (diffuse alveolar hemorrhage), intracranial bleed, gastro-intestinal hemorrhage (gross hematemesis or hematochezia), gross hematuria or uncontrolled epistaxis irrespective of the amount of blood loss, within the prior 3 days.
• On mechanical ventilation for > 96 consecutive hours.
• Serum platelet count < 50,000/Microliters (uL). Transfusion of platelets to achieve a level > 50,000/uL is not allowed for eligibility.
• Serum fibrinogen < 150 mg/dl. Transfusion of fresh frozen plasma or cryoprecipitate to achieve a level > 150 mg/dl is not allowed for eligibility.
• Positive blood culture for a bacterial pathogen within the prior 24 hours prior to study entry, and/or the presence of bacterial pneumonia.
• Hemodynamic instability as defined by a requirement for 2 or more vasopressors (not including renal-doses of dopamine).
• Concurrent use of Extracorporeal membrane oxygenation (ECMO).
• Patients with a previously known hypersensitivity reaction to defibrotide, or any of its excipients.
• Females who are pregnant or breastfeeding.
• History of cerebrovascular accident (i.e. thrombotic or hemorrhagic stroke) within 3 months prior to study entry.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jazz Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Gregory Yanik

OTHER

Sponsor Role: lead

Responsible Party

Gregory Yanik

Professor of Pediatric Hematology/Oncology, Professor of Pediatrics and Communicable Diseases and Professor of Internal Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Gregory Yanik, MD

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Locations

University of Michigan

Ann Arbor, Michigan, United States

Countries

United States

References

Frame D, Scappaticci GB, Braun TM, Maliarik M, Sisson TH, Pipe SW, Lawrence DA, Richardson PG, Holinstat M, Hyzy RC, Kaul DR, Gregg KS, Lama VN, Yanik GA. Defibrotide Therapy for SARS-CoV-2 ARDS. Chest. 2022 Aug;162(2):346-355. doi: 10.1016/j.chest.2022.03.046. Epub 2022 Apr 9.

Reference Type: DERIVED

PMID: 35413279 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

HUM00182089

Identifier Type: -

Identifier Source: org_study_id