Clinical trial NCT05396755: Biliary Interventions in Critically Ill Patients With Secondary Sclerosing Cholangitis (BISCIT)
Official title: Biliary Interventions in Critically Ill Patients With Secondary Sclerosing Cholangitis - a Multicenter, Randomized Controlled, Parallel Group Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Secondary Sclerosing Cholangitis
Keywords: biliary intervention
endoscopic therapy
endoscopic retrograde cholangiography
Lead sponsor: Hannover Medical School
Sponsor class: OTHER
Collaborators: name: German Research Foundation
First posted: 2022-05-31
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized, open-label, controlled, parallel group, multicenter
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: occurrence of death
timeFrame: up to week 48
measure: necessity of liver transplantation
timeFrame: up to week 48
measure: occurrence of cholangiosepsis (defined by SEPSIS-3 criteria and diagnosis of acute cholangitis according to the Tokyo Guidelines), whatever occurs first.
timeFrame: up to week 48
Secondary outcomes:
measure: Laboratory parameters (bilirubin in µmol/L) as change from baseline
timeFrame: week 24
measure: Laboratory parameters (alkaline phosphatase in U/L) as change from baseline
timeFrame: week 24
measure: Laboratory parameters (gamma-glutamyltransferase) as change from baseline
timeFrame: week 24
measure: Laboratory parameters (aspartate aminotransferase in U/L) as change from baseline
timeFrame: week 24
measure: Laboratory parameters (alanine aminotransferase in U/L) as change from baseline
timeFrame: week 24
measure: Laboratory parameters (lactate dehydrogenase in U/L) as change from baseline
timeFrame: week 24
measure: Laboratory parameters (glutamate dehydrogenase in U/L) as change from baseline
timeFrame: week 24
measure: Laboratory parameters (creatinine in µmol/L) as change from baseline
timeFrame: week 24
measure: Laboratory parameters (c-reactive protein in mg/L) as change from baseline
timeFrame: week 24
measure: Laboratory parameters (cholinesterase in kU/L) as change from baseline
timeFrame: week 24
measure: To analyze course of liver function (Model for endstage liver disease score as changes from baseline)
timeFrame: week 24
measure: 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)
timeFrame: week 24
measure: To analyze the need for anti-infective therapy (antibiotic treatment) in the different study arms
timeFrame: week 24
measure: Occurrence of unplanned hospital admissions (necessity and days free of hospital care within 6 months)
timeFrame: week 24
Other outcomes:
measure: Changes in specific signatures in biliary microbiome
timeFrame: day1, week 8, week 16, week 24
measure: To analyze the extent of biliary tract damage at magnetic resonance cholangiopancreatography (MRCP) in the different study arms.
timeFrame: week 24
measure: Occurrence of infections: cholangitis, cholecystitis
timeFrame: up to week 48
measure: Occurrence of ERC-related complications: bleeding, perforation, pancreatitis, cholangitis,
timeFrame: day1, week 8, week 16, week 24
measure: occurrence of serious adverse events
timeFrame: day1, week 8, week 16, week 24, week 32, week 40, week 48
Locations:
city: Hannover
country: Germany
facility: Hannover Medical School
state: Lower Saxony
Study officials:
affiliation: Hannover Medical School, Department of Gastroenterology, Hepatology and Endocrinology
name: Hans H. Wedemeyer, Prof.
role: PRINCIPAL_INVESTIGATOR
References: