Prospective, Multicenter Cohort Study on Primary Biliary Cholangitis

Primary Biliary Cholangitis Clinical Trial

— PBC-Cohort  

Official title:

Prospective, Multicenter Cohort Study on Primary Biliary Cholangitis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04076527
• Other study ID #: 2.0
• Status: Recruiting
• Start date: September 19, 2019
• Est. completion date: March 2024

Study information

• Verified date: June 2023
• Source: University of Leipzig
• Contact: Thomas Berg, Prof.Dr.
• Phone: +49 341 97 12 330
• Email: thomas.berg[@]medizin.uni-leipzig.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 1200
• Est. completion date: March 2024
• Est. primary completion date: March 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cholangitis
• Liver Cirrhosis, Biliary
• PBC
• Primary Biliary Cholangitis

Intervention

Drug:
• UDCA
Routine data is collected for UDCA therapy.
• Ocaliva
Routine data is collected for OCA therapy.

Locations

Country	Name	City	State
Germany	University Hospital Aachen	Aachen
Germany	Charité - Campus Benjamin Franklin	Berlin
Germany	Charité-Campus Virchow-Klinikum	Berlin
Germany	Internal Practice	Berlin
Germany	Liver Center Checkpoint	Berlin
Germany	MVZ Gastroenterology	Berlin
Germany	Hospital Chemnitz	Chemnitz
Germany	University Hospital Cologne	Cologne
Germany	Internal Practice	Dornstadt
Germany	MVZ Düsseldorf	Düsseldorf
Germany	University hospital Düsseldorf	Düsseldorf
Germany	University Hospital Erlangen	Erlangen
Germany	St. Josef- Hospital Kupferdreh	Essen
Germany	University Hospital Essen	Essen
Germany	Internal Practice	Frankfurt
Germany	University Hospital J.W. Goethe- Universität	Frankfurt am Main
Germany	University Hospital Freiburg	Freiburg
Germany	University Hospital Gießen	Gießen
Germany	Gastroenerological-Oncological Practice	Halle
Germany	University Hospital Halle	Halle
Germany	Liver Center Hamburg - Asklepios Clinic St. Georg	Hamburg
Germany	Internal Practice	Hameln
Germany	MHH	Hannover
Germany	University Hospital Heidelberg	Heidelberg
Germany	Gastroenerological Practice	Herne
Germany	University hospital Saarland	Homburg
Germany	University Hospital Jena	Jena
Germany	Gastroenerological Practice	Kassel
Germany	Center for Gastroenterology and Hepatology Kiel	Kiel
Germany	University Hospital Schleswig-Holstein Campus Kiel	Kiel
Germany	Eugastro - Gastroenerological Practice	Leipzig
Germany	University Hospital Leipzig	Leipzig
Germany	MVZ Leverkusen	Leverkusen
Germany	University hospital Schleswig-Holstein	Lübeck
Germany	Internal Practice Hepatology	Magdeburg
Germany	University hospital Magdeburg	Magdeburg
Germany	University Hospital Mainz	Mainz
Germany	University Hospital Mannheim	Mannheim
Germany	Hospital LMU	Munich
Germany	Liver Center Munich	Munich
Germany	Technical University - Klinikum rechts der Isar	Munich
Germany	University Hospital Münster	Münster
Germany	Hospital Nuremberg	Nuremberg
Germany	Internal Practice	Potsdam
Germany	University Hospital Regensburg	Regensburg
Germany	Diakonie-Klinikum Schwäbisch Hall	Schwäbisch Hall
Germany	Internal Practice	Schwerin
Germany	University Hospital Tübingen	Tübingen
Germany	University Hospital Ulm	Ulm
Germany	St. Josefs-Hospital	Wiesbaden

Sponsors (10)

Lead Sponsor	Collaborator
University of Leipzig	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Hannover Medical School, Institute for Interdisciplinary Medicine, Hamburg, Intercept Pharma Europe Limited (IPEL), Leberhilfe Projekt gUG, Cologne, Medical care center for Gastroenterology, Berlin, RWTH Aachen University, University Hospital Erlangen, Zentrum für Klinische Studien Leipzig

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Systematic registry	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.	from baseline to 36 months after baseline (observational period)
Secondary	Comprehensive clinical characterization of German PBC patients	i.e. demographics, biochemical markers, ultrasound, transient elastography, stage of the disease	from baseline to 36 months after baseline
Secondary	Characterization of PBC therapies	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.	from baseline to 36 months after baseline
Secondary	Treatment response to PBC therapies after 12 months and during longer courses of application	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.: frequency of hepatic decompensation (occurrence of variceal hemorrhage, ascites, encephalopathy, and/or hepatocellular carcinoma),; frequency of liver transplants,; frequency of deaths in total and from a liver-related cause, and; 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.	from baseline to 12 months after baseline and to 36 months after baseline
Secondary	Application and analyses of existing prognostic PBC scores to provide information on patients' prognosis.	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.	from baseline to 36 months after baseline
Secondary	Concomitant Medications	Assessment of selected concomitant medications (e.g. symptomatic treatment of pru-ritus)	from baseline to 36 months after baseline
Secondary	Concomitant Autoimmune Diseases	Assessment of selected concomitant autoimmune diseases (e.g. overlap syndrome with autoimmune hepatitis)	from baseline to 36 months after baseline
Secondary	Concomitant Non-Autoimmune Diseases	Assessment of selected concomitant non-autoimmune diseases (i.e. cardiovascular disease, non-alcoholic fatty liver disease, metabolic syndrome, chronic kidney diseases)	from baseline to 36 months after baseline