Prospective, Multicenter Cohort Study on Primary Biliary Cholangitis (PBC-Cohort)

June 6, 2023 updated by: Thomas Berg, University of Leipzig
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Estimated)

1200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Germany
      • Aachen, Germany
        • Recruiting
        • University Hospital Aachen
        • Contact:
          • Christian Trautwein, Prof.Dr.
      • Berlin, Germany
        • Recruiting
        • Charite - Campus Benjamin Franklin
        • Contact:
          • Marion Muche, Dr.
      • Berlin, Germany
        • Recruiting
        • Charité-Campus Virchow-Klinikum
        • Contact:
          • Tobias Müller, Dr.
      • Berlin, Germany
        • Recruiting
        • Internal Practice
        • Contact:
          • Uwe Naumann, Dr.
      • Berlin, Germany
        • Not yet recruiting
        • Liver Center Checkpoint
        • Contact:
          • Renate Heyne, Dr.
      • Berlin, Germany
        • Recruiting
        • MVZ Gastroenterology
        • Contact:
          • Wolf Peter Hofmann, Prof. Dr.
      • Chemnitz, Germany
        • Recruiting
        • Hospital Chemnitz
        • Contact:
          • Ulrich Stölzel, Prof. Dr.
      • Cologne, Germany
        • Withdrawn
        • University Hospital Cologne
      • Dornstadt, Germany
        • Recruiting
        • Internal Practice
        • Contact:
          • Nektarios Dikopoulos, Prof. Dr.
      • Düsseldorf, Germany
        • Withdrawn
        • MVZ Düsseldorf
      • Düsseldorf, Germany
        • Not yet recruiting
        • University Hospital Düsseldorf
        • Contact:
          • Hans Bock, Prof.
      • Erlangen, Germany
        • Recruiting
        • University Hospital Erlangen
        • Contact:
          • Andreas Kremer, Dr. Dr.
      • Essen, Germany
        • Recruiting
        • St. Josef- Hospital Kupferdreh
        • Contact:
          • Susanne Beckebaum, Prof. Dr.
      • Essen, Germany
        • Not yet recruiting
        • University Hospital Essen
        • Contact:
          • Sandra Christoph, Dr
      • Frankfurt, Germany
        • Withdrawn
        • Internal Practice
      • Frankfurt am Main, Germany
        • Recruiting
        • University Hospital J.W. Goethe- Universität
        • Contact:
          • Stefan Zeuzem, Prof. Dr.
      • Freiburg, Germany
        • Recruiting
        • University Hospital Freiburg
        • Contact:
          • Christoph Neumann-Haefelin, Dr.
      • Gießen, Germany
        • Recruiting
        • University Hospital Gießen
        • Contact:
          • Elke Roeb, Prof. Dr.
      • Halle, Germany
        • Recruiting
        • Gastroenerological-Oncological Practice
        • Contact:
          • Rüdiger Behrens, Dr
      • Halle, Germany
        • Recruiting
        • University Hospital Halle
        • Contact:
          • Greinert, Dr.
      • Hamburg, Germany
        • Withdrawn
        • Liver Center Hamburg - Asklepios Clinic St. Georg
      • Hameln, Germany
        • Withdrawn
        • Internal Practice
      • Hannover, Germany
        • Recruiting
        • MHH
        • Contact:
          • Heike Bantel, Prof. Dr.
      • Heidelberg, Germany
        • Recruiting
        • University Hospital Heidelberg
        • Contact:
          • Theresa Hippchen, Dr.
      • Herne, Germany
        • Recruiting
        • Gastroenerological Practice
        • Contact:
          • Matthias Hinz, Dr.
      • Homburg, Germany
        • Recruiting
        • University hospital Saarland
        • Contact:
          • Marcin Krawczyk, Prof. Dr.
      • Jena, Germany
        • Recruiting
        • University Hospital Jena
        • Contact:
          • Philipp Reuken, Dr.
      • Kassel, Germany
        • Withdrawn
        • Gastroenerological Practice
      • Kiel, Germany
        • Recruiting
        • University Hospital Schleswig-Holstein Campus Kiel
        • Contact:
          • Rainer Günther, Dr.
      • Kiel, Germany
        • Recruiting
        • Center for Gastroenterology and Hepatology Kiel
        • Contact:
          • Holger Hinrichsen, MD
      • Leipzig, Germany
        • Recruiting
        • University Hospital Leipzig
        • Contact:
          • Thomas Berg, Prof. Dr.
        • Contact:
          • Johannes Wiegand, Prof.Dr.
      • Leipzig, Germany, 04129
        • Recruiting
        • Eugastro - Gastroenerological Practice
        • Contact:
          • Ingolf Schiefke, Prof.
      • Leverkusen, Germany
        • Recruiting
        • MVZ Leverkusen
        • Contact:
          • Karl- Georg Simon, Dr.
      • Lübeck, Germany
        • Recruiting
        • University Hospital Schleswig-Holstein
        • Contact:
          • Henrike Dobbermann, Dr.
      • Magdeburg, Germany
        • Recruiting
        • Internal Practice Hepatology
        • Contact:
          • Kerstin Stein, Dr.
      • Magdeburg, Germany
        • Recruiting
        • University Hospital Magdeburg
        • Contact:
          • Verena Keitel-Anselmino, Prof. Dr.
      • Mainz, Germany
        • Recruiting
        • University Hospital Mainz
        • Contact:
          • Jörn Schattenberg, PD Dr
      • Mannheim, Germany
        • Recruiting
        • University Hospital Mannheim
        • Contact:
          • Andreas Teufel, Prof.Dr.Dr.
      • Munich, Germany
        • Recruiting
        • Hospital LMU
        • Contact:
          • Gerald Denk, PD Dr
      • Munich, Germany
        • Withdrawn
        • Liver Center Munich
      • Munich, Germany
        • Recruiting
        • Technical University - Klinikum rechts der Isar
        • Contact:
          • Ursula Tanase, Dr.
      • Münster, Germany
        • Recruiting
        • University Hospital Münster
        • Contact:
          • Hauke Heinzow, Prof. Dr.
      • Nuremberg, Germany
        • Recruiting
        • Hospital Nuremberg
        • Contact:
          • Andreas Weber, Dr.
      • Potsdam, Germany
        • Recruiting
        • Internal Practice
        • Contact:
          • Harald Grümmer, Dr.
      • Regensburg, Germany
        • Withdrawn
        • University Hospital Regensburg
      • Schwerin, Germany
        • Withdrawn
        • Internal Practice
      • Schwäbisch Hall, Germany
        • Withdrawn
        • Diakonie-Klinikum Schwäbisch Hall
      • Tübingen, Germany
        • Recruiting
        • University Hospital Tübingen
        • Contact:
          • Christoph Berg, Prof. Dr.
      • Ulm, Germany
        • Not yet recruiting
        • University Hospital Ulm
        • Contact:
          • Eugen Zizer, Dr.
      • Wiesbaden, Germany
        • Recruiting
        • St. Josefs-Hospital
        • Contact:
          • Christoph Sarrazin, Prof. Dr.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

The patients will be recruited in gastroenterology specialized practices and outpatient clinics which provide routine treatment for PBC patients.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Group 1 - Incomplete Responder
  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.
Drug: UDCA
Routine data is collected for UDCA therapy.
Other Names:
  • ursodeoxycholic acid
Drug: Ocaliva
Routine data is collected for OCA therapy.
Other Names:
  • obeticholic acid
Group 2 - Responder
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.
Drug: UDCA
Routine data is collected for UDCA therapy.
Other Names:
  • ursodeoxycholic acid
Group 3
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.
Drug: UDCA
Routine data is collected for UDCA therapy.
Other Names:
  • ursodeoxycholic acid
Drug: Ocaliva
Routine data is collected for OCA therapy.
Other Names:
  • obeticholic acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Systematic registry
Time Frame: 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.
from baseline to 36 months after baseline (observational period)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comprehensive clinical characterization of German PBC patients
Time Frame: from baseline to 36 months after baseline
i.e. demographics, biochemical markers, ultrasound, transient elastography, stage of the disease
from baseline to 36 months after baseline
Characterization of PBC therapies
Time Frame: 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.
from baseline to 36 months after baseline
Treatment response to PBC therapies after 12 months and during longer courses of application
Time Frame: 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.
from baseline to 12 months after baseline and to 36 months after baseline
Application and analyses of existing prognostic PBC scores to provide information on patients' prognosis.
Time Frame: 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.
from baseline to 36 months after baseline
Concomitant Medications
Time Frame: from baseline to 36 months after baseline
Assessment of selected concomitant medications (e.g. symptomatic treatment of pru-ritus)
from baseline to 36 months after baseline
Concomitant Autoimmune Diseases
Time Frame: from baseline to 36 months after baseline
Assessment of selected concomitant autoimmune diseases (e.g. overlap syndrome with autoimmune hepatitis)
from baseline to 36 months after baseline
Concomitant Non-Autoimmune Diseases
Time Frame: 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)
from baseline to 36 months after baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Leipzig

Collaborators

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

Investigators

  • Study Chair: Thomas Berg, Prof.Dr., University of Leipzig
  • Principal Investigator: Johannes Wiegand, Prof.Dr., University of Leipzig
  • Principal Investigator: Christian Trautwein, Prof.Dr., RWTH Aachen University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 19, 2019

Primary Completion (Estimated)

March 1, 2024

Study Completion (Estimated)

March 1, 2024

Study Registration Dates

First Submitted

August 29, 2019

First Submitted That Met QC Criteria

August 29, 2019

First Posted (Actual)

September 3, 2019

Study Record Updates

Last Update Posted (Actual)

June 7, 2023

Last Update Submitted That Met QC Criteria

June 6, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2.0

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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