Clinical trial NCT03032016: European VOD Registry
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®
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hepatic Veno-Occlusive Disease
Keywords: VOD
Defibrotide
Defitelio
Registry
SOS
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: European Society for Blood and Marrow Transplantation
First posted: 2017-01-26
Enrollment: 176
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The patients will be selected by the treating physicians working in hospitals being part of the European society for Bone Marrow Transplantation network.

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.

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.

Primary outcomes:
measure: Incidence rate of specific SAE of interest
timeFrame: over 12 months
Secondary outcomes:
measure: Describe the population treated
timeFrame: Enrolment
measure: GvHD incidence
timeFrame: over 12 months
measure: Survival
timeFrame: over 12 months
measure: VOD/MOF Resolution
timeFrame: over 12 months
Other outcomes:
Locations:
city: Angers
country: France
facility: CHRU Angers, Maladies du Sang
city: Bordeaux
country: France
facility: CHU Bordeaux Groupe hospitalier Pellegrin Enfants
city: Clermont Ferrand
country: France
facility: CHU d'Estaing
city: Lille
country: France
facility: CHRU de Lille
city: Lille
country: France
facility: Hôpital Jeanne de Flandre
city: Limoges
country: France
facility: CHRU Limoges
city: Lyon
country: France
facility: IHOP
city: Mare aux Daims
country: France
facility: Hôpital d'enfants de la Timone
city: Marseille
country: France
facility: Institut Paoli Calmette
city: Montpellier
country: France
facility: CHU Lapeyronie
city: Nantes
country: France
facility: CHU Nantes
city: Nice
country: France
facility: Hôpital de l'ARCHET
city: Paris
country: France
facility: Hôpital Saint Antoine
city: Paris
country: France
facility: Hôpital Robert Debré
city: Paris
country: France
facility: Hôpital Tenon
city: Paris
country: France
facility: Institut Curie
city: Pessac
country: France
facility: Hôpital Haut Leveque
city: Poitiers
country: France
facility: Hôpital de la Miletrie
city: Strasbourg
country: France
facility: CHU Hautepierre
city: Toulouse
country: France
facility: IUTC Oncopole
city: Villejuif
country: France
facility: Institut Gustave Roussy (Pediatrics)
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Bergamo
country: Italy
facility: Azienda Ospedaliera Papa Giovanni XXIII
city: Firenze
country: Italy
facility: UO Oncoematologia Ospedale Pediatrico Mayer
city: Florence
country: Italy
facility: Ospedale di Careggi
city: Genova
country: Italy
facility: Institute G. Gaslini
city: Milano
country: Italy
facility: Ospedale Ca' Granda Ospedale Maggiore di Milano
city: Milano
country: Italy
facility: Ospedale di Niguarda Ca' Granda
city: Milan
country: Italy
facility: Ospedale San Raffaele
city: Padova
country: Italy
facility: Clinica di oncoematologia pediatrica
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Perugia
country: Italy
facility: Ospedale Santa Maria de la Misericorda
city: Potenza
country: Italy
facility: Ospedale San Carlo
city: Roma
country: Italy
facility: IRRCS Ospedale Pediatrico Bambino Gesù
city: Roma
country: Italy
facility: Universita Cattolica S. Cuore
city: Rome
country: Italy
facility: La Sapienza University Hospital
city: Torino
country: Italy
facility: AOU Citta della salute e delle Scienza
city: Torino
country: Italy
facility: Ospedale Infantile Regina Margherita
city: Trieste
country: Italy
facility: Istituto per l'Infanzia IRCCS Burlo Garofolo
city: Udine
country: Italy
facility: Clinica Ematologica-Azienda Ospedaliero Universitaria
city: Verona
country: Italy
facility: Policlinico G.B. Rossi, Clinica di Oncoematologia Pediatrica
city: Lisboa
country: Portugal
facility: Inst. Portugues Oncologia o Lisboa
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
city: Bristol
country: United Kingdom
facility: Bristol Royal Hospital for Children
city: London
country: United Kingdom
facility: Great Ormond Street Hospital Children's Charity
city: London
country: United Kingdom
facility: Imperial College
city: London
country: United Kingdom
facility: St George's Hospital
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
city: Newcastle Upon Tyne
country: United Kingdom
facility: Great North Children's Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
city: Oxford
country: United Kingdom
facility: John Radccliffe Children's Hospital
city: Plymouth
country: United Kingdom
facility: Plymouth Hospitals NHS Trust
Study officials:
References:
citation: Mohty M, Battista ML, Blaise D, Calore E, Cesaro S, Maximova N, Perruccio K, Renard C, Wynn R, Zecca M, Labopin M, Hanvesakul R, Amber V, Ryan RJ, Lawson S, Ciceri F. A multicentre, multinational, prospective, observational registry study of defibrotide in patients diagnosed with veno-occlusive disease/sinusoidal obstruction syndrome after haematopoietic cell transplantation: an EBMT study. Bone Marrow Transplant. 2021 Oct;56(10):2454-2463. doi: 10.1038/s41409-021-01265-2. Epub 2021 May 31.