Clinical trial NCT04076527: Prospective, Multicenter Cohort Study on Primary Biliary Cholangitis
Official title: Prospective, Multicenter Cohort Study on Primary Biliary Cholangitis
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: PBC
Primary Biliary Cholangitis
Keywords: ursodeoxycholic acid
UDCA
obeticholic acid
OCALIVA
Cohort
observational study
Bezafibrat
Budesonide
Lead sponsor: University of Leipzig
Sponsor class: OTHER
Collaborators: name: RWTH Aachen University
name: Zentrum für Klinische Studien Leipzig
name: Intercept Pharma Europe Limited (IPEL)
name: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: University Hospital Erlangen
name: Medical care center for Gastroenterology, Berlin
name: Institute for Interdisciplinary Medicine, Hamburg
name: Leberhilfe Projekt gUG, Cologne
name: Hannover Medical School
First posted: 2019-09-03
Enrollment: 1200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Systematic registry
timeFrame: from baseline to 36 months after baseline (observational period)
Secondary outcomes:
measure: Comprehensive clinical characterization of German PBC patients
timeFrame: from baseline to 36 months after baseline
measure: Characterization of PBC therapies
timeFrame: from baseline to 36 months after baseline
measure: Treatment response to PBC therapies after 12 months and during longer courses of application
timeFrame: from baseline to 12 months after baseline and to 36 months after baseline
measure: Application and analyses of existing prognostic PBC scores to provide information on patients' prognosis.
timeFrame: from baseline to 36 months after baseline
measure: Concomitant Medications
timeFrame: from baseline to 36 months after baseline
measure: Concomitant Autoimmune Diseases
timeFrame: from baseline to 36 months after baseline
measure: Concomitant Non-Autoimmune Diseases
timeFrame: from baseline to 36 months after baseline
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: University Hospital Aachen
city: Berlin
country: Germany
facility: Charité - Campus Benjamin Franklin
city: Berlin
country: Germany
facility: Charité-Campus Virchow-Klinikum
city: Berlin
country: Germany
facility: Internal Practice
city: Berlin
country: Germany
facility: Liver Center Checkpoint
city: Berlin
country: Germany
facility: MVZ Gastroenterology
city: Chemnitz
country: Germany
facility: Hospital Chemnitz
city: Cologne
country: Germany
facility: University Hospital Cologne
city: Dornstadt
country: Germany
facility: Internal Practice
city: Düsseldorf
country: Germany
facility: MVZ Düsseldorf
city: Düsseldorf
country: Germany
facility: University hospital Düsseldorf
city: Erlangen
country: Germany
facility: University Hospital Erlangen
city: Essen
country: Germany
facility: St. Josef- Hospital Kupferdreh
city: Essen
country: Germany
facility: University Hospital Essen
city: Frankfurt am Main
country: Germany
facility: University Hospital J.W. Goethe- Universität
city: Frankfurt
country: Germany
facility: Internal Practice
city: Freiburg
country: Germany
facility: University Hospital Freiburg
city: Gießen
country: Germany
facility: University Hospital Gießen
city: Halle
country: Germany
facility: Gastroenerological-Oncological Practice
city: Halle
country: Germany
facility: University Hospital Halle
city: Hamburg
country: Germany
facility: Liver Center Hamburg - Asklepios Clinic St. Georg
city: Hameln
country: Germany
facility: Internal Practice
city: Hannover
country: Germany
facility: MHH
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg
city: Herne
country: Germany
facility: Gastroenerological Practice
city: Homburg
country: Germany
facility: University hospital Saarland
city: Jena
country: Germany
facility: University Hospital Jena
city: Kassel
country: Germany
facility: Gastroenerological Practice
city: Kiel
country: Germany
facility: Center for Gastroenterology and Hepatology Kiel
city: Kiel
country: Germany
facility: University Hospital Schleswig-Holstein Campus Kiel
city: Leipzig
country: Germany
facility: Eugastro - Gastroenerological Practice
city: Leipzig
country: Germany
facility: University Hospital Leipzig
city: Leverkusen
country: Germany
facility: MVZ Leverkusen
city: Lübeck
country: Germany
facility: University hospital Schleswig-Holstein
city: Magdeburg
country: Germany
facility: Internal Practice Hepatology
city: Magdeburg
country: Germany
facility: University hospital Magdeburg
city: Mainz
country: Germany
facility: University Hospital Mainz
city: Mannheim
country: Germany
facility: University Hospital Mannheim
city: Munich
country: Germany
facility: Hospital LMU
city: Munich
country: Germany
facility: Liver Center Munich
city: Munich
country: Germany
facility: Technical University - Klinikum rechts der Isar
city: Münster
country: Germany
facility: University Hospital Münster
city: Nuremberg
country: Germany
facility: Hospital Nuremberg
city: Potsdam
country: Germany
facility: Internal Practice
city: Regensburg
country: Germany
facility: University Hospital Regensburg
city: Schwerin
country: Germany
facility: Internal Practice
city: Schwäbisch Hall
country: Germany
facility: Diakonie-Klinikum Schwäbisch Hall
city: Tübingen
country: Germany
facility: University Hospital Tübingen
city: Ulm
country: Germany
facility: University Hospital Ulm
city: Wiesbaden
country: Germany
facility: St. Josefs-Hospital
Study officials:
affiliation: University of Leipzig
name: Thomas Berg, Prof.Dr.
role: STUDY_CHAIR
affiliation: University of Leipzig
name: Johannes Wiegand, Prof.Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: RWTH Aachen University
name: Christian Trautwein, Prof.Dr.
role: PRINCIPAL_INVESTIGATOR
References: