Last updated on July 2018

European VOD Registry

Brief description of study

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), the pharmaceutical company that manufactures Defitelio (Gentium, a Jazz Pharmaceuticals Company) - as a specific obligation (SOB) - has been 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), which is being coordinated through the European Society for Blood and Marrow Transplantation (EBMT). Following appropriate consent, data from patients who undergo haematopoietic stem cell transplantation are routinely collected at the local centre for the EBMT database. For this study, the sites are being asked to collect additional anonymised clinical data from patients who develop this complication or who have been treated with Defitelio for other reasons than sVOD. The study simply requires collection of data which is already recorded in the patient charts, but not routinely collected.

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 Study Description

Defitelio has been granted a Marketing Authorisation in Europe under exceptional circumstances. 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 a specific obligation (SOB), Gentium has been required 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 is a multi-centre, multinational and prospective observational disease registry of patients with severe hepatic VOD following HSCT, to record patients treated with Defitelio or supportive care.

Gentium has been required to ensure that information regarding all potential and identified risks reported in the most recent version of the Risk Management Plan is being collected.

Hepatic VOD is one of the most common life-threatening regimen-related toxicities that constitutes a barrier to successful allogeneic and autologous HSCT. VOD is characterised by rapid weight gain, painful hepatomegaly, hyperbilirubinemia/jaundice, and ascites/fluid retention, without other identifiable causes for liver disease (Richardson, 2012). In a recent survey on 135 studies performed between 1997 and October 2007, the overall mean incidence of VOD has been reported to be 13.7% with a lower rate of 9.6% when Baltimore criteria were applied (Coppell, 2010).

The severe form of the disease, usually associated with pulmonary dysfunction and/or renal dysfunction (ie, multi-organ failure, MOF), with or without encephalopathy, and a mortality rate of more than 80% by 100 days after HSCT, is reported to occur in about 40%-60% of VOD patients, that is approximately 3-5% of transplanted patients.

Given the low incidence of sVOD and the varying size of bone marrow transplant centres in EU, in order to collect meaningful clinical data, the registry will be conducted in European transplant centres only in which the overall number of transplant is at least 100 per year.

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 treated with Defitelio and to compare these rates with those occurring in a similar population not treated with Defitelio.

Secondary objectives are:

  • To describe the population treated with Defibrotide and controls (age, gender, ethnicity, 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 and in controls
  • To determine survival by Day+100 post-HSCT, overall mortality and mortality due to VOD in patients treated with Defibrotide and in controls
  • To determine the rate of VOD/MOF resolution any time after treatment initiation in patients treated with Defibrotide and in controls.

Clinical Study Identifier: NCT03032016

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Natalia Maximova, MD

Istituto per l'Infanzia IRCCS Burlo Garofolo
Trieste, Italy