Hepatic Veno-Occlusive Disease
Conditions
Keywords
VOD
Brief 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.
Interventions
DRUGDefibrotide
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.
Sponsors
Jazz Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Survival by Day+100 Post Stem Cell Transplant or Chemotherapy | Day +100 from HSCT or 100 days from start of chemotherapy |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Defibrotide Defibrotide 25 mg/kg day given in 4 divided doses approximately every 6 hours | 1,154 |
| Total | 1,154 |
Baseline characteristics
| Characteristic | Defibrotide |
|---|---|
| Age, Continuous | 19.32 years STANDARD_DEVIATION 20.004 |
| Sex: Female, Male Female | 503 Participants |
| Sex: Female, Male Male | 651 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 166 / 1,154 |
| serious Total, serious adverse events | 598 / 1,154 |
Outcome results
Primary
Survival by Day+100 Post Stem Cell Transplant or Chemotherapy
Time frame: Day +100 from HSCT or 100 days from start of chemotherapy
Population: ITT Efficacy Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Defibrotide | Survival by Day+100 Post Stem Cell Transplant or Chemotherapy | 49.9 Percentage of participants alive |