Prospective, Multicenter Cohort Study on Primary Biliary Cholangitis
- Registration Number
- NCT04076527
- Lead Sponsor
- University of Leipzig
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1200
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Age ≥ 18 years
-
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.
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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.
-
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Medication-based treatment with at least one drug approved in Germany for the treatment of PBC
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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
-
Patients must meet criteria of one of the cohorts (group 1/2/3) within this NIS according to design
-
written statement of informed consent
Current participation in a phase I to IV interventional clinical trial for PBC or participation in another PBC registry.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Group 1 - Incomplete Responder Ocaliva 1. Primary Incomplete Responder: PBC patients demonstrating an insufficient response to the standard therapy with ursodeoxycholic acid (UDCA) after a minimum of 12 months of treatment (Paris II criteria). 2. Secondary Incomplete Responder: PBC patients demonstrating a satisfactory initial response to UDCA after a minimum of 12 months of treatment (Paris II criteria) followed by a re-increase of ALP ≥1.5 ULN, or AST ≥1.5 ULN, or bilirubin \>1 mg/dl at any later time point during continuous UDCA-treatment. Group 3 Ocaliva Patients newly diagnosed for PBC receiving an approved PBC therapy for the first time. Patients are considered to be newly diagnosed if the initial diagnosis took place no later than six months prior to inclusion into the study. Group 1 - Incomplete Responder UDCA 1. Primary Incomplete Responder: PBC patients demonstrating an insufficient response to the standard therapy with ursodeoxycholic acid (UDCA) after a minimum of 12 months of treatment (Paris II criteria). 2. Secondary Incomplete Responder: PBC patients demonstrating a satisfactory initial response to UDCA after a minimum of 12 months of treatment (Paris II criteria) followed by a re-increase of ALP ≥1.5 ULN, or AST ≥1.5 ULN, or bilirubin \>1 mg/dl at any later time point during continuous UDCA-treatment. Group 2 - Responder UDCA PBC patients demonstrating a satisfactory initial and contin-ued response to UDCA after a minimum of 12 months of treatment (Paris II criteria) without a re-increase of ALP ≥1.5 ULN, or AST ≥1.5 ULN, or bilirubin \>1 mg/dl at any later time point during continuous UDCA-treatment. Group 3 UDCA Patients newly diagnosed for PBC receiving an approved PBC therapy for the first time. Patients are considered to be newly diagnosed if the initial diagnosis took place no later than six months prior to inclusion into the study.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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)
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)
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.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.
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.Concomitant Medications from baseline to 36 months after baseline Assessment of selected concomitant medications (e.g. symptomatic treatment of pru-ritus)
Trial Locations
- Locations (44)
Charité-Campus Virchow-Klinikum
🇩🇪Berlin, Germany
University Hospital Aachen
🇩🇪Aachen, Germany
Charité - Campus Benjamin Franklin
🇩🇪Berlin, Germany
Internal Practice
🇩🇪Schwerin, Germany
MVZ Gastroenterology
🇩🇪Berlin, Germany
University Hospital Cologne
🇩🇪Cologne, Germany
Hospital Chemnitz
🇩🇪Chemnitz, Germany
Liver Center Checkpoint
🇩🇪Berlin, Germany
MVZ Düsseldorf
🇩🇪Düsseldorf, Germany
University hospital Düsseldorf
🇩🇪Düsseldorf, Germany
University Hospital Erlangen
🇩🇪Erlangen, Germany
St. Josef- Hospital Kupferdreh
🇩🇪Essen, Germany
University Hospital Gießen
🇩🇪Gießen, Germany
University Hospital J.W. Goethe- Universität
🇩🇪Frankfurt am Main, Germany
University Hospital Freiburg
🇩🇪Freiburg, Germany
University Hospital Essen
🇩🇪Essen, Germany
Gastroenerological-Oncological Practice
🇩🇪Halle, Germany
University Hospital Halle
🇩🇪Halle, Germany
Liver Center Hamburg - Asklepios Clinic St. Georg
🇩🇪Hamburg, Germany
MHH
🇩🇪Hannover, Germany
University Hospital Heidelberg
🇩🇪Heidelberg, Germany
Gastroenerological Practice
🇩🇪Kassel, Germany
University hospital Saarland
🇩🇪Homburg, Germany
University Hospital Jena
🇩🇪Jena, Germany
Center for Gastroenterology and Hepatology Kiel
🇩🇪Kiel, Germany
University Hospital Schleswig-Holstein Campus Kiel
🇩🇪Kiel, Germany
Eugastro - Gastroenerological Practice
🇩🇪Leipzig, Germany
Internal Practice Hepatology
🇩🇪Magdeburg, Germany
University hospital Schleswig-Holstein
🇩🇪Lübeck, Germany
MVZ Leverkusen
🇩🇪Leverkusen, Germany
University Hospital Leipzig
🇩🇪Leipzig, Germany
University hospital Magdeburg
🇩🇪Magdeburg, Germany
University Hospital Mainz
🇩🇪Mainz, Germany
Hospital LMU
🇩🇪Munich, Germany
University Hospital Mannheim
🇩🇪Mannheim, Germany
Liver Center Munich
🇩🇪Munich, Germany
Technical University - Klinikum rechts der Isar
🇩🇪Munich, Germany
University Hospital Münster
🇩🇪Münster, Germany
Hospital Nuremberg
🇩🇪Nuremberg, Germany
University Hospital Regensburg
🇩🇪Regensburg, Germany
University Hospital Ulm
🇩🇪Ulm, Germany
St. Josefs-Hospital
🇩🇪Wiesbaden, Germany
Diakonie-Klinikum Schwäbisch Hall
🇩🇪Schwäbisch Hall, Germany
University Hospital Tübingen
🇩🇪Tübingen, Germany