Defibrotide for Patients With Hepatic Veno-occlusive Disease: A Treatment IND Study (Treatment IND)
This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
First received: February 25, 2008
Last updated: April 11, 2016
Last verified: April 2016
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.
Hepatic Veno-Occlusive Disease
||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||Defibrotide for Patients With Hepatic Veno-occlusive Disease: A Treatment IND Study
Primary Outcome Measures:
- Survival at Day +100 or from HSCT or 100 days from start of chemotherapy [ Time Frame: Day +100 from HSCT or 100 days from start of chemotherapy ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Tolerability & Safety Data from Patients with VOD [ Time Frame: From time of Consent to 30 Days Post of Last Administration of Study Drug ] [ Designated as safety issue: Yes ]
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||July 2016 (Final data collection date for primary outcome measure)
Defibrotide 25 mg/kg day given in 4 divided doses approximately every 6 hours
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.
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
Entry criteria include the following:
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.
- Patient must also provide written informed consent.
- 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.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00628498
||William Tappe, M.D.
||Paul Richardson, M.D.
||Dana-Farber Cancer Institute
Richardson PG, Murakami C, Jin Z, Warren D, Momtaz P, Hoppensteadt D, Elias AD, Antin JH, Soiffer R, Spitzer T, Avigan D, Bearman SI, Martin PL, Kurtzberg J, Vredenburgh J, Chen AR, Arai S, Vogelsang G, McDonald GB, Guinan EC. Multi-institutional use of defibrotide in 88 patients after stem cell transplantation with severe veno-occlusive disease and multisystem organ failure: response without significant toxicity in a high-risk population and factors predictive of outcome. Blood. 2002 Dec 15;100(13):4337-43. Epub 2002 Aug 1.
History of Changes
|Other Study ID Numbers:
|Study First Received:
||February 25, 2008
||April 11, 2016
||United States: Food and Drug Administration
Keywords provided by Jazz Pharmaceuticals:
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on May 26, 2016
Hepatic Veno-Occlusive Disease
Digestive System Diseases
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors