Defibrotide for Patients With Hepatic Veno-occlusive Disease: A Treatment IND Study
Condition: Hepatic Veno-Occlusive Disease
MeSH terms: Hepatic Veno-Occlusive Disease
Intervention: Defibrotide; Defibrotide
Intervention description: Defibrotide is a single-stranded polydeoxyribonucleotide derived from porcine intestinal mucosa by controlled depolymerisation. Defibrotide has a complex mechanism of action with antithrombotic, anti-ischemic, anti-inflammatory, anti-adhesive and thrombolytic properties but no significant systemic anti-coagulant effects.
Defibrotide is dose intravenously as a 2-hour infusion every 6 hours at a dose of 25 mg/kg/day. Recommended duration of therapy is 21 days.
Intervention MeSH terms: Defibrotide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1206.0
Sex: All
Healthy volunteers: No
Keywords: VOD

Summary:

      Single arm, open-label study to provide Defibrotide to patients diagnosed with VOD.
      Defibrotide is no longer available though the Emergency Use IND mechanism (also known as
      compassionate use, or single patient named use). This protocol is the only mechanism by which
      Defibrotide can be made available to patients in the U.S.
    

Eligibility criteria:

        Inclusion Criteria:

        Entry criteria include the following:

          1. Clinical diagnosis of VOD, made by Baltimore Criteria, Modified Seattle Criteria, or
             biopsy proven:

             1.1 Baltimore Criteria- Bilirubin ≥2 mg/dL and at least 2 of the following clinical
             findings:

               -  Ascites (radiographic or physical exam)

               -  Weight gain of ≥5% compared to the day of conditioning-- if this value is not
                  available, the weight on the date of admission to the SCT unit may be used)

               -  Hepatomegaly; increased over baseline.

             1.2 Modified Seattle Criteria: At least two of the following

               -  Bilirubin ≥2 mg/dL

               -  Ascites (radiographic or physical exam) and/or weight gain ≥5% above baseline
                  weight (defined as weight on the first day of conditioning- if this value is not
                  available, the weight on the date of admission to the SCT unit may be used)

               -  hepatomegaly increased over baseline

             1.3 Patients that do not meet the Baltimore Criteria or Modified Seattle Criteria and
             have biopsy proven VOD are eligible.

          2. Patient must also provide written informed consent.

        Exclusion Criteria:

          -  Use of any medication which increases the risk of hemorrhage is disallowed. Use of
             heparin or other anticoagulants is disallowed within 12 hours unless being used for
             routine central venous line management, fibrinolytic instillation for central venous
             line occlusion, intermittent dialysis or ultrafiltration of CVVH.

          -  Clinically significant uncontrolled acute bleeding, defined as hemorrhage requiring >
             15 cc/kg of packed red blood cells (e.g., a pediatric patient weighing 20 kg and
             requiring > 300cc of packed red blood cells/24 hours, or an adult patient weighing 70
             kg and requiring >3 units of packed red blood cells/24 hours) to replace blood loss,
             OR bleeding from a site which in the Investigator's opinion constitutes a potential
             life-threatening source (e.g. pulmonary hemorrhage or CNS bleeding), irrespective of
             amount of blood loss, at any point from the date of SCT through the date of severe VOD
             diagnosis.

          -  Hemodynamic instability as defined by a requirement for multiple pressors, or
             inability to maintain mean arterial pressure (for children: to maintain mean arterial
             pressure within 1 standard deviation of age-adjusted levels) with single pressor
             support.

          -  Woman who are pregnant.