Biliary Interventions in Critically Ill Patients With Secondary Sclerosing Cholangitis (BISCIT) (BISCIT)

Biliary Interventions in Critically Ill Patients With Secondary Sclerosing Cholangitis - a Multicenter, Randomized Controlled, Parallel Group Trial

This is a randomized, open-label, controlled, parallel group, multicenter clinical trial. Patients with confirmed secondary sclerosing cholangitis (SSC-CIP) will be randomized either in the intervention group undergoing scheduled invasive evaluation of the biliary tract or in the control group treated with non-interventional standard of care to demonstrate that programmed endoscopic therapy compared to a conservative strategy reduces the occurrence of treatment failures.

Study Overview

• Status: Terminated
• Conditions: Secondary Sclerosing Cholangitis
• Intervention / Treatment: Procedure: Endoscopic retrograde cholangiography (ERC)

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Lower Saxony
    • Hannover, Lower Saxony, Germany, 30625
      • Hannover Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Patients have to fulfill all of the following inclusion criteria to be eligible for participation in this study:

1. Men, women*, inter/divers, age ≥18 and ≤ 80 years (conscious or unconscious patients may be included)
2. Signed written informed consent obtained by patient or legal representative in case of unconscious patient
3. Willingness to comply with treatment and follow-up procedures
4. Suspected SSC-CIP = episode of critical illness and intensive care unit treatment > 3 days within last 12 months
5. SSC-CIP is confirmed by ERC, (if the first ERC is performed at baseline, the patient may be considered as screening failure if the diagnosis is not confirmed)
6. Elevation of bilirubin ≥ 2.5 upper limit of normal (ULN) at Screening
7. Elevation of alkaline phosphatase (AP) or gamma-glutamyl-transferase (GGT) > 2.5 ULN or elevation of both at Screening

8. *Women without childbearing potential defined as follows:

   • at least 6 weeks after surgical sterilization by bilateral tubal ligation or bilateral oophorectomy or
   • hysterectomy or uterine agenesis or
   • ≥ 50 years and in postmenopausal state > 1 year or

   • < 50 years and in postmenopausal state > 1 year with serum Follicle Stimulating Hormone (FSH) > 40 IU/l and serum estrogen < 30 ng/l or a negative estrogen test, both at screening or

     *Women of childbearing potential:

   • who are practicing sexual abstinence (periodic abstinence and withdrawal are not acceptable) or
   • who have sexual relationships with female partners only and/or with sterile male partners or
   • who are sexually active with fertile male partner, have a negative pregnancy test during screening and agree to use reliable methods of contraception (failure rate of < 1% per year) from the time of screening until end of the clinical trial.

Exclusion Criteria:

1. Patient is too unstable to undergo ERC
2. Inclusion in any other intervention trial within the last 30 days
3. Pregnancy or lactation period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: interventional; The intervention group undergoes scheduled invasive evaluation of the biliary tract with endoscopic retrograde cholangiography (ERC) with biliary interventions (i.e. therapeutic ERC) every 8 weeks for 6 months.	Procedure: Endoscopic retrograde cholangiography (ERC); invasive evaluation of the biliary tract with ERC and endoscopic interventions every 8 weeks until 6 months (24 weeks)
No Intervention: control; The control group receives non-interventional standard of care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
occurrence of death	The primary endpoint is the failure rate defined as a composite endpoint consisting of; occurrence of death or; necessity of liver transplantation or; occurrence of cholangiosepsis (defined by SEPSIS-3 criteria and diagnosis of acute cholangitis according to the Tokyo Guidelines), whatever occurs first.	up to week 48
necessity of liver transplantation	The primary endpoint is the failure rate defined as a composite endpoint consisting of; occurrence of death or; necessity of liver transplantation or; occurrence of cholangiosepsis (defined by SEPSIS-3 criteria and diagnosis of acute cholangitis according to the Tokyo Guidelines), whatever occurs first.	up to week 48
occurrence of cholangiosepsis (defined by SEPSIS-3 criteria and diagnosis of acute cholangitis according to the Tokyo Guidelines), whatever occurs first.	The primary endpoint is the failure rate defined as a composite endpoint consisting of; occurrence of death or; necessity of liver transplantation or; occurrence of cholangiosepsis (defined by SEPSIS-3 criteria and diagnosis of acute cholangitis according to the Tokyo Guidelines), whatever occurs first.	up to week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Laboratory parameters (bilirubin in µmol/L) as change from baseline		week 24
Laboratory parameters (alkaline phosphatase in U/L) as change from baseline		week 24
Laboratory parameters (gamma-glutamyltransferase) as change from baseline		week 24
Laboratory parameters (aspartate aminotransferase in U/L) as change from baseline		week 24
Laboratory parameters (alanine aminotransferase in U/L) as change from baseline		week 24
Laboratory parameters (lactate dehydrogenase in U/L) as change from baseline		week 24
Laboratory parameters (glutamate dehydrogenase in U/L) as change from baseline		week 24
Laboratory parameters (creatinine in µmol/L) as change from baseline		week 24
Laboratory parameters (c-reactive protein in mg/L) as change from baseline		week 24
Laboratory parameters (cholinesterase in kU/L) as change from baseline		week 24
To analyze course of liver function (Model for endstage liver disease score as changes from baseline)	Model for End-Stage Liver Disease (MELD) score 0-40 points with higher values indicating increasing impairment of liver function	week 24
Occurrence of unplanned Intensive care unit (ICU) admissions (necessity and days free of: intensive care unit care, invasive ventilation, renal replacement therapy, vasopressors within 6 months)		week 24
To analyze the need for anti-infective therapy (antibiotic treatment) in the different study arms	Necessity of treatment with anti-infective medication (= treament with antibiotic oral or intravenously for acute cholangitis) (yes/no)	week 24
Occurrence of unplanned hospital admissions (necessity and days free of hospital care within 6 months)		week 24

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in specific signatures in biliary microbiome		day1, week 8, week 16, week 24
To analyze the extent of biliary tract damage at magnetic resonance cholangiopancreatography (MRCP) in the different study arms.	Extent of bile duct damage at 6-months MRCP compared to baseline as determined by central radiology reading	week 24
Occurrence of infections: cholangitis, cholecystitis		up to week 48
Occurrence of ERC-related complications: bleeding, perforation, pancreatitis, cholangitis,		day1, week 8, week 16, week 24
occurrence of serious adverse events	population	day1, week 8, week 16, week 24, week 32, week 40, week 48

Collaborators and Investigators

• Sponsor: Hannover Medical School
• Collaborators: German Research Foundation
• Investigators: Principal Investigator: Hans H. Wedemeyer, Prof., Hannover Medical School, Department of Gastroenterology, Hepatology and Endocrinology

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2022
• Primary Completion (Actual): September 14, 2023
• Study Completion (Actual): September 14, 2023

Study Registration Dates

• First Submitted: May 3, 2022
• First Submitted That Met QC Criteria: May 25, 2022
• First Posted (Actual): May 31, 2022

Study Record Updates

• Last Update Posted (Actual): October 11, 2023
• Last Update Submitted That Met QC Criteria: October 9, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: biliary intervention; endoscopic therapy; endoscopic retrograde cholangiography
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplastic Processes; Biliary Tract Diseases; Bile Duct Diseases; Neoplasm Metastasis; Cholangitis; Cholangitis, Sclerosing
• Other Study ID Numbers: BISCIT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No