Defibrotide for Patients With Hepatic Veno-occlusive Disease: A Treatment IND Study
Defibrotide for Patients With Hepatic Veno-occlusive Disease: A Treatment IND Study
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.
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.