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

Study Overview
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Brief Summary
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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.

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

Conditions
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Secondary Sclerosing Cholangitis

Intervention / Treatment
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* Procedure: Endoscopic retrograde cholangiography (ERC)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients have to fulfill all of the following inclusion criteria to be eligible for participation in this study: Men, women*, inter/divers, age ≥18 and ≤ 80 years (conscious or unconscious patients may be included) Signed written informed consent obtained by patient or legal representative in case of unconscious patient Willingness to comply with treatment and follow-up procedures Suspected SSC-CIP = episode of critical illness and intensive care unit treatment > 3 days within last 12 months 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) Elevation of bilirubin ≥ 2.5 upper limit of normal (ULN) at Screening Elevation of alkaline phosphatase (AP) or gamma-glutamyl-transferase (GGT) > 2.5 ULN or elevation of both at Screening *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: Patient is too unstable to undergo ERC Inclusion in any other intervention trial within the last 30 days Pregnancy or lactation period

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: randomized, open-label, controlled, parallel group, multicenter
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: interventional<br>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)<br>* invasive evaluation of the biliary tract with ERC and endoscopic interventions every 8 weeks until 6 months (24 weeks)<br>|
| No Intervention: control<br>The control group receives non-interventional standard of care. | |

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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biliary intervention, endoscopic therapy, endoscopic retrograde cholangiography