Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT03717792 |
| Other study ID # |
VALID |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 1, 2010 |
| Est. completion date |
December 31, 2027 |
Study information
| Verified date |
October 2021 |
| Source |
University Hospital, Bonn |
| Contact |
Michael Praktiknjo, MD |
| Phone |
+4922828715770 |
| Email |
michael.praktiknjo[@]ukbonn.de |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Background Vascular liver disorders (VALDI) are rare diseases, for which knowledge on risk
factors, appropriate methods of diagnosis, effect of therapy and prognosis still need to be
improved.
Aim of the study This project aims to study risk factors, methods of detection, therapy and
prognosis in order to elaborate and disseminate updated recommendations for the optimal
management of patients with VALDI.
Design of the study Data on patients will be collected from baseline (the date of diagnosis)
up to 3 years. During this period, data on clinical condition, laboratory results, diagnostic
tests, interventions and outcome will be collected anonymously using standardised review of
medical charts by one special trained investigator. Only patients with VALDI are eligible to
participate.
Description:
Background Vascular liver disorders (VALDI), including Budd-Chiari syndrome (BCS),
non-cirrhotic vascular liver disorders (VLD) and idiopathic non-cirrhotic portal hypertension
(INCPH) are rare diseases that mainly affect children and young adults. These diseases are
related to alterations in hepatic macrocirculation (hepatic veins, portal vein) or
microcirculation (small portal veins, sinusoids or both) in the absence of cirrhosis. Even
though various types of VALDI differ in presentation and etiology, they still share in part
underlying causes and mechanisms.
Most studies on VALDI aim at clarifying etiology, natural history and management have been
retrospective and are based on a relatively small number of patients. A European Union FP5
funded project from 2003 to 2005 (EN-Vie) performed several prospective observational
studies, in which 157 patients with BCS and 102 patients with acute VLD were included.
However, chronic VLD and INCPH were not included in the EN-Vie project.
Prothrombotic disorders are found in 65 to 85% of patients with BCS or VLD, but only 20-40%
of INCPH patients. By contrast, chronic inflammatory conditions are more frequently
encountered in patients with INCPH and VLD than in those with BCS. There is evidence for a
significant genetic influence in patients with INCPH. Still, in over 40% of INCPH patients
the cause remains unknown. The reason for these differences in causes among the various
VALDI, as well as the mechanisms for specific sites of thrombosis according to the underlying
conditions remain obscure.
VALDI complications mostly consist in gastrointestinal bleeding, refractory ascites,
bacterial infections, hepatocellular carcinoma, and ultimately liver failure. Such
complications are observed in approximately 60%, 20% and 15% of patients with BCS, VLD and
INCPH, respectively. The incidence of bleeding related to portal hypertension is as high as
20 % patients-year in patients with VLD or INCPH. Recurrent or extensive thrombosis may
jeopardize liver transplantation or lead to high morbidity and mortality complications, e.g.
intestinal infarction. Moreover, complications related to the underlying disorders
superimpose on those directly related to VALDI, and particularly so for acquired blood
diseases.
The outcome of VALDI has been recently evaluated in large prospective European studies. (a) A
recent update on BCS cohort showed a good outcome with a strategy comprising anticoagulation
therapy and, when needed, angioplasty, stenting, TIPS, or liver transplantation. Similarly,
anticoagulation at the early stage of VLD has been shown to prevent thrombus extension and,
in 40% of the cases, to be accompanied by recanalization. The results of these studies have
had an impact much beyond the field of primary VALDI. Actually it proved instrumental in
developing novel and promising strategies with anticoagulation for the management of
cirrhosis, a chronic parenchymal liver disease much more common than VALDI. (b) By contrast,
for patients with chronic VLD prospective follow-up data are not available. Retrospective
data suggest that anticoagulation is not associated with excessive bleeding. However, in
patients at risk for gastrointestinal bleeding due to portal hypertension and a mild or
moderate risk of recurrent thrombosis, the benefit-risk ratio of anticoagulation therapy is
particularly unclear. Furthermore, the time point, if any, when anticoagulation shifts from a
beneficial to a detrimental effect, has not been explored. (c) The natural history of INCPH
evaluated in only 3 retrospective surveys indicates that the incidence of extrahepatic VLD is
surprisingly high, whereas advanced liver disease or hepatopulmonary syndrome may occur in up
to 15% of patients. Therefore, anticoagulation therapy, TIPS and liver transplantation have
also been proposed in patients with INCPH.
• Although recent studies have provided a marked impetus to the field of clinical research on
VALDI, crucial information is still lacking, particularly in the areas of etiology, inherited
factors, and treatment. Etiology is still unknown in 40% of the patients; genetic data are
incomplete, therapeutic trials, although badly needed have never been performed, so that
recommendations for treatments (with potentially fatal side effects in these high bleeding
risk population) rely on limited data.
Aims Identification of incident and prevalent cases of VALDI as a basis for the
implementation of future studies, namely interventional randomised control studies,
observational studies, and prognostic studies including the identification of new biomarkers
for these diseases through the analysis of the prospectively recorded data according to
consensual management.
This study will allow to obtain:
Incidence estimates Increased numbers of patients candidates to future studies Homogeneous,
robust and consistent criteria for diagnosis, follow-up and treatment, allowing clearly
defined cohorts of patients to be constituted.
Identify the collections of biological and tissue samples stored in the same conditions, for
future the identification of novel biomarkers. Samples will have to be linked to high quality
clinical, laboratory and imaging data for translational studies
Create a basis for continuous collections for a large variety of research purposes including:
Prognostic research Systems biology research including (epi)genetic research Clinical trials
using various design adapted for rare diseases Health care policies and cost-effectiveness
studies
