Biliary Interventions in Critically Ill Patients With Secondary Sclerosing Cholangitis - a Multicenter, Randomized Controlled, Parallel Group Trial
Trial Snapshot
- Phase
- Not Applicable
- Status
- Terminated
- Sponsor
- Hannover Medical School
- Enrollment
- 1
- Locations
- 1
- Primary Endpoint
- occurrence of cholangiosepsis (defined by SEPSIS-3 criteria and diagnosis of acute cholangitis according to the Tokyo Guidelines), whatever occurs first.
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
control
The control group receives non-interventional standard of care.
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.
Intervention: Endoscopic retrograde cholangiography (ERC) (Procedure)
Outcomes
Primary Outcomes
occurrence of cholangiosepsis (defined by SEPSIS-3 criteria and diagnosis of acute cholangitis according to the Tokyo Guidelines), whatever occurs first.
Time Frame: up to week 48
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.
necessity of liver transplantation
Time Frame: up to week 48
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.
occurrence of death
Time Frame: up to week 48
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.
Secondary Outcomes
- Laboratory parameters (creatinine in µmol/L) as change from baseline(week 24)
- 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)
- To analyze course of liver function (Model for endstage liver disease score as changes 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 (glutamate dehydrogenase in U/L) as change from baseline(week 24)
- Laboratory parameters (c-reactive protein in mg/L) as change from baseline(week 24)
- Laboratory parameters (gamma-glutamyltransferase) as change from baseline(week 24)
- Laboratory parameters (lactate dehydrogenase in U/L) as change from baseline(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)
- Laboratory parameters (cholinesterase in kU/L) as change from baseline(week 24)
- To analyze the need for anti-infective therapy (antibiotic treatment) in the different study arms(week 24)
- Occurrence of unplanned hospital admissions (necessity and days free of hospital care within 6 months)(week 24)