European VOD Registry

Study Overview
=================
Brief Summary
-----------------
Following the licencing of a new drug, Defitelio®, indicated for the treatment of severe Veno-Occlusive Disease of the liver (sVOD), a rare but serious complication of haematopoietic stem cell transplantation (HSCT), as a specific obligation (SOB), the manufacture and marketing Authorisation Holder (MHA) (Gentium, a Jazz Pharmaceuticals Company) was required by PRAC (Pharmacovigilance Risk Assessment Committee) to set up a disease registry to collect safety and outcome data, and to assess patterns of utilization of Defitelio® in the post-approval setting. This registry is a Post Authorization Safety Study (PASS), is being coordinated in collaboration with the European Society for Blood and Marrow Transplantation (EBMT). For this study, anonymised clinical data are being collected from patients who develop VOD and and treated with and patients who have been treated with Defitelio® for conditions other than sVOD. The study DOES NOT involve decisions about treatment, which are clinical decisions, but merely collection of data for patients who develop this complication, whether or not they receive treatment and for patients who are treated with Defitelio® for any other reasons.The study DOES NOT involve decisions about treatment, which are clinical decisions, but merely collection of data for patients who develop this complication, whether or not they receive treatment and for patients who are treated with Defitelio® for any other reasons.

Detailed Description
-----------------
Defitelio® was granted a Marketing Authorisation in Europe under exceptional circumstances on 18 October 2013. Defitelio® is indicated for the treatment of severe hepatic Veno-Occlusive Disease (sVOD) also known as sinusoidal obstruction syndrome (SOS) in haematopoietic stem-cell transplantation (HSCT) therapy. It is indicated in adults and in adolescents, children and infants over 1 month of age. As required by the risk management plan, Gentium set up a disease registry to collect safety and outcome data, and to assess patterns of utilization of Defitelio® in the post-approval setting. This is a multi-centre, multinational and prospective observational (non-interventional) disease registry of patients with severe hepatic VOD following HSCT and treated with Defitelio®. The registry will be conducted in European transplant centres that are members of the European Society for Blood and Marrow Transplantation (EBMT). The main objective of the registry is to assess the incidence rate of specific SAEs (Serious Adverse Events) of interest (including fatalities) in patients with severe hepatic VOD post-HSCT treated with Defitelio®. Secondary objectives are: To describe the population treated with Defibrotide (age, gender, patients with pre-existing liver or severe renal insufficiency; patient with intrinsic lung disease) To determine the incidence rate of multiorgan failure (MOF) and Graft versus host disease (GvHD) in adult and paediatric patients receiving Defibrotide. To determine survival by Day+100 post-HSCT, overall mortality and mortality due to VOD in patients treated with Defibrotide. To determine the rate of VOD and VOD with MOF resolution any time after treatment initiation in patients treated with Defibrotide.

Official Title
-----------------
A Multi-centre, Multinational, Prospective Observational Registry to Collect Safety and Outcome Data in Patients Diagnosed With Severe Hepatic Veno-occlusive Disease (VOD) Following Hematopoietic Stem Cell Transplantation (HSCT) and Treated With Defitelio®

Conditions
-----------------
Hepatic Veno-Occlusive Disease

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients undergoing hematopoietic stem cell transplantation and diagnosed with severe hepatic VOD, who agree to participate in the study (Main population). Patients treated with defibrotide for another condition than severe hepatic VOD (Secondary population) in the scope of hematopoietic stem cell transplantation . Exclusion Criteria: There will not be any specific exclusion criteria; however contraindications, special warnings and precautions for use as detailed in the SPC will have to be considered by the treating physician.

Ages Eligible for Study
-----------------
Minimum Age: 1 Month

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| sVOD patient treated with defibrotide<br>Patient diagnosed with severe hepatic VOD and treated with defibrotide | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence rate of specific SAE of interest | Assess the incidence rate of specific SAEs of interest (including fatalities) in patients with severe hepatic VOD post-HSCT treated with Defitelio® | over 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Describe the population treated | To describe the population treated with Defitelio® (age, gender, patients with pre-existing liver or severe renal insufficiency; patient with intrinsic lung disease) | Enrolment | 
| GvHD incidence | Determine the incidence rate of Graft versus host disease (GvHD) in adult and paediatric patients receiving Defitelio® | over 12 months | 
| Survival | To determine survival by Day+100 post-HSCT, overall mortality and mortality due to VOD in patients treated with Defitelio® | over 12 months | 
| VOD/MOF Resolution | To determine the rate of VOD and VOD with MOF resolution any time after treatment initiation in patients treated with Defitelio® | over 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
VOD, Defibrotide, Defitelio, Registry, SOS