PBC, Primary Biliary Cholangitis
Conditions
Keywords
ursodeoxycholic acid, UDCA, obeticholic acid, OCALIVA, Cohort, observational study, Bezafibrat, Budesonide
Brief summary
The German PBC Cohort is a multi-centric, observational (non-interventional) study with three parallel groups. The main objective of this observational study is to describe the course of Primary biliary cholangitis (PBC) in patients in Germany under routine treatment with approved drugs. Therefore, the effectiveness and safety/tolerability of PBC treatment options in a real-life setting will be evaluated.
Detailed description
Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic liver disease. The course of the disease is characterized by a slow destruction of bile ducts, and progressive cholestasis. Prognosis depends on the development of cirrhosis and its complications. Ursodeoxycholic acid (UDCA) has been established as standard therapy for PBC and improves patients' long-term outcome. However, UDCA is not a uniformly effective drug, and the prognosis of PBC patients insufficiently responding to treatment is markedly worse. For patients with suboptimal treatment response to UDCA obeticholic acid (OCA) as newly approved medication (OCALIVA®) is available as second line treatment. Due to the low prevalence and the slowly progressive course of the disease it is very difficult to investigate the prognosis of subgroups of PBC patients or to evaluate the effectivness of therapeutic interventions on clinical outcomes. Therefore, several national or international registries (UK-PBC Consortium or the Global PBC Study Group) were founded to better characterize the clinical course of PBC patients. Since in Germany a registry for PBC does not exist, the German PBC Cohort is being implemented as observational study to collect data on treatment progress and success in clinical routine that reflects real world conditions in Germany as closely as possible. The effectiveness and safety/tolerability of PBC treatment options (UDCA as standard therapy and second-line treatment options like OCALIVA in case of inadequate UDCA treatment response) will be evaluated. In approximatly 40 sites in Germany routine data is collected. There are no specifications for the diagnosis, therapy and monitoring of the PBC patients. The documentation of the routine data is carried out alongside with guideline recommended treatment intervals of the patients. Furthermore, a critical criterion for the German PBC Cohort study is the involvement of a sufficient number of gastroenterology specialized practices and outpatient clinics that have consciously not been selected based on the strict specifications of a clinical trial and which provide routine treatment for PBC patients. In addition, patient access is designed to be open. Data will be collected on patient groups that represent a majority of the PBC patients in Germany, but who are not being investigated in clinical trials.
Interventions
Sponsors
RWTH Aachen University
Zentrum für Klinische Studien Leipzig
Intercept Pharma Europe Limited (IPEL)
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
University Hospital Erlangen
Medical care center for Gastroenterology, Berlin
Institute for Interdisciplinary Medicine, Hamburg
Leberhilfe Projekt gUG, Cologne
Hannover Medical School
University of Leipzig
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years 2. Diagnosis of PBC PBC diagnosis (consistent with AASLD and EASL practice guidelines), as demonstrated by the presence of at least two of the following three diagnostic factors: * History of elevated ALP levels for 6 months. * Positive anti-mitochondrial antibody (AMA) titer or if AMA negative or in low titer (\<1:80) =\> PBC-specific antibodies: * anti-GP210 and/or * anti-SP100 and/or * antibodies against the major M2 components \[PDC-E2, 2-oxo-glutaric acid dehydrogenase complex (OADC-E2), branched-chain-2-oxo-acid-dehydrogenase complex, (BCOADC-E2)\]. * Liver biopsy consistent with PBC. 3. Medication-based treatment with at least one drug approved in Germany for the treatment of PBC 4. Availability of all following essential parameters at the initial diagnosis of PBC prior to the initiation of treatment with UDCA, 12 months after initiation of UDCA and if applicable at time point of secondary incomplete response: * Platelet count * Alkaline Phosphatase (ALP) * Total Bilirubin * Aspartate aminotransferase (AST/GOT) * Age at initial diagnosis of PBC 5. Patients must meet criteria of one of the cohorts (group 1/2/3) within this NIS according to design 6. written statement of informed consent
Exclusion criteria
Current participation in a phase I to IV interventional clinical trial for PBC or participation in another PBC registry.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Systematic registry | from baseline to 36 months after baseline (observational period) | A primary outcome measure is not applicable as usual, since this data acquisition is performed to built a newly developed systematic registry which serves to describe - for the first time in Germany - the characteristics and the recent state of usual clinical care of the respective population. Within the 18 months of recruitment and 3 years of individual follow-up for every patient regular analyses will be performed and published, based on a statistical analysis plan which may be yearly updated on request to address the main questions of the responsible PBC consortium. After the end of data acquisition hepatologic scientists may apply with detailed proposals to further use available data. A scientific consortium will than decided on further analyses of data. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Characterization of PBC therapies | from baseline to 36 months after baseline | Characterization of UDCA as first line therapy and characterization of approved second-line treatment options such as OCALIVA. Furthermore, safety data on the PBC medications used will be systematically gathered and reported on high-level aggregation with regard to any causality with PBC treatment per cohort. The respective results will be reviewed against the known safety profiles. |
| Treatment response to PBC therapies after 12 months and during longer courses of application | from baseline to 12 months after baseline and to 36 months after baseline | To evaluate the natural progression under PBC drug therapy with respect to response to treatment changes in laboratory results (as ratios of the upper/lower limits of normal or differences to BL values) and characteristics of liver function will be described, e.g.: 1. frequency of hepatic decompensation (occurrence of variceal hemorrhage, ascites, encephalopathy, and/or hepatocellular carcinoma), 2. frequency of liver transplants, 3. frequency of deaths in total and from a liver-related cause, and 4. details on further events of special interest, e.g. for the first time serum bilirubin \> ULN and/or alkaline phosphatase \> 1.5 ULN, or transient elastography \> 9.6 kPa. |
| Application and analyses of existing prognostic PBC scores to provide information on patients' prognosis. | from baseline to 36 months after baseline | Details on typical therapeutic measures in treating PBC and patient compliance will be presented. This allows making a statement on quality of PBC treatment in Germany. Effectiveness will be assessed per cohort and compared between physicians' practices and hospital outpatient departments, aggregating data over all participating sites of the respective structure of health care. This refers to GLOBE score and/or Paris II criteria, frequency of hepatic decompensation or frequency of abnormal surrogate parameter (i.e. alkaline phosphatase, bilirubin, ALAT, ASAT or transient elastography). The respective results will be discussed against the results provided from clinical trials to verify everyday suitability of the different PBC therapies. |
| Comprehensive clinical characterization of German PBC patients | from baseline to 36 months after baseline | i.e. demographics, biochemical markers, ultrasound, transient elastography, stage of the disease |
| Concomitant Autoimmune Diseases | from baseline to 36 months after baseline | Assessment of selected concomitant autoimmune diseases (e.g. overlap syndrome with autoimmune hepatitis) |
| Concomitant Non-Autoimmune Diseases | from baseline to 36 months after baseline | Assessment of selected concomitant non-autoimmune diseases (i.e. cardiovascular disease, non-alcoholic fatty liver disease, metabolic syndrome, chronic kidney diseases) |
| Concomitant Medications | from baseline to 36 months after baseline | Assessment of selected concomitant medications (e.g. symptomatic treatment of pru-ritus) |
Countries
Germany
Contacts
Primary ContactThomas Berg, Prof.Dr.
Backup ContactJohannes Wiegand, Prof.Dr.
Outcome results
None listed