Short-term Stenting Versus Balloon Dilatation for Dominant Strictures in Primary Sclerosing Cholangitis

Multicenter Randomized Trial Comparing Short-term Stenting Versus Balloon Dilatation for Dominant Strictures in Primary Sclerosing Cholangitis

Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of the biliary tract of unknown origin. Around 50% of patients develop during their disease course narrowing of the main bile duct with corresponding increase in symptoms such as itching, jaundice and abdominal pain. These narrowings can be treated by balloon dilatation or temporary insertion of a plastic endoprosthesis. However, it is not known which of these two therapeutic modalities is best. This study aims to compare both techniques in order to determine which is best in terms of postponing recurrence of the narrowing, safety and costs.

Study Overview

• Status: Unknown
• Conditions: Primary Sclerosing Cholangitis
• Intervention / Treatment: Procedure: plastic endoprosthesis; Procedure: balloon dilatation

Detailed Description

Rationale:

Primary sclerosing cholangitis is a chronic progressive fibro-obliterative disease of the biliary tree leading to biliary cirrhosis. During its course, dominant strictures occur in approximately 50% of patients. These can be accompanied by lead worsening of symptoms and jaundice and are an indication for endoscopic treatment. The best form of treatment, either balloon dilatation or short-term stent placement, has never been formally investigated.

Objective:

Primary:

To compare the efficacy of single session balloon dilatation versus short-term stent placement in non-advanced PSC patients with regard to re-intervention free recurrence rate at two years.

Secondary:

To compare the short term efficacy of single balloon dilatation versus short-term stenting with regard to improvement of cholestatic symptoms, biochemical cholestasis, and quality of life in non-endstage PSC patients at three months; to compare the safety of single balloon dilatation session versus short-term stenting in non advanced PSC patients during two years.

Study design: This is a multicenter, open-label, randomized intervention study.

Study population:

Non-advanced primary sclerosing cholangitis subjects with progression of cholestatic complaints from the outpatient population of the seven participating centres.

Main study parameters/endpoints:

1. Difference in re-intervention free survival time between both groups at two years.
2. Change in semi-quantitative scoring of cholestatic symptoms (pruritus, right upper quadrant pain, fatigue) from baseline at three months.
3. Change in total bilirubin, alkaline phosphatase, and yGT from baseline at 3 months.
4. Safety: adverse events, clinical laboratory values, vital signs.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

Currently, both interventions belong to standard patient care armamentarium. Burden for the patient exists in slightly more regular follow-up visits for two years (three-monthly instead of every 3-4 months) to their treating centre. ERCP is associated with a low mortality (<0.5 %) and acceptable morbidity (overall 5%). Most dreaded complications are severe post-ERCP pancreatitis (<2%) and suppurative cholangitis (<2%). From the available retrospective literature data the incidence of these complications does not seem to differ between the two treatment modalities. ERCP will only be performed when there is a clearcut clinical indication anyway.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium
    • Recruiting
    • UZLeuven
    • Contact: Werner van Steenbergen, Prof; Phone Number: +3216340749; Email: werner.vansteenbergen@uzleuven.be
    • Contact: Natalie van den Ende, BsC; Phone Number: +32 16340749; Email: natalie.vandenende@uzleuven.be
• Netherlands
  • Amsterdam, Netherlands, 1100 DE
    • Recruiting
    • Academic Medical Center
    • Contact: Cyriel Ponsioen, MD PhD; Phone Number: +31 20 5666012; Email: c.y.ponsioen@amc.uva.nl
    • Contact: Florien Toxopeus, MsC; Phone Number: +31 20 5669111; Email: f.m.toxopeus@amc.uva.nl
    • Principal Investigator: Cyriel Ponsioen, MD PhD
• Norway
  • Oslo, Norway, N-0027
    • Recruiting
    • Rikshospitalet
    • Contact: Lars Aabakken, Prof.; Phone Number: +47 23072387; Email: lars.aabakken@medisin.uio.no
    • Contact: Vemund Paulsen, MD; Phone Number: +47 23070000; Email: vemund.paulsen@meisin.uio.no
    • Principal Investigator: Lars Aabakken, MD PhD
• Sweden
  • Stockholm, Sweden, 141 86
    • Recruiting
    • Karolinska Institute
    • Contact: Annika Bergquist, prof; Phone Number: +46 8 58582465; Email: annika.bergquist@ki.se
    • Contact: Urban Arnelo, dr; Phone Number: +46 8 58582465; Email: urban.arnelo@ki.se
    • Principal Investigator: Annika Bergquist, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• PSC ascertained with MRCP, ERCP, PTC and/or liver biopsy or
• PSC highly suspected and to be confirmed with present ERCP
• Age between 18-75 years
• Total bilirubin > 3x ULN or rsie in alkaline phosphatase or bilirubin > 50% together with increase in cholestatic complaints

Exclusion Criteria:

• Prior stenting or balloon-dilatation within last 6 months
• Clinical signs serious suppurative cholangitis reflected by either fever > 39.0 °C, tachycardia, leukocytosis and elevated CRP, or fever > 38,5 C together with purulent bile found during ERCP.
• Change of ursodeoxycholic acid therapy shorter than two months ago.
• Inability to give written informed consent
• Signs of biliary cirrhosis Child-Pugh B or C
• Estimated transplant-free survival shorter than 2 years as calculated by a Mayo score < 2
• Serious suspicion of cholangiocarcinoma, reflected by an imaging study suggestive of metastasis, MRCP with mass lesion with contrast enhancement, rise in CA19.9 of > 63 U/ml with an absolute value > 130 U/ml 14 .
• Signs of current malignancy other than basocellular skin carcinoma.
• Inability to give informed consent.
• Life expectancy < 24 months.
• Use of antibiotics in previous 4 weeks.

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
Active Comparator: short-term stenting; one 10 Fr Plastic endoprosthesis or 2 7 Fr plastic endoprosthesis inserted through dominant stricture(s), to be extracted after 1-2 weeks	Procedure: plastic endoprosthesis; one 10 Fr Plastic endoprosthesis or 2 7 Fr plastic endoprosthesis inserted through dominant stricture(s), to be extracted after 1-2 weeks; Other Names: plastic stent
Active Comparator: balloon dilatation; 4 cm 6 mm biliary dilatation balloon to be inflated for 2 minutes in dominant stricture(s)	Procedure: balloon dilatation; 4 cm 6 mm biliary dilatation balloon to be inflated for 2 minutes in dominant stricture(s); Other Names: biliary dilatation balloon

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
recurrence-free interval of the primary dominant stricture	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of patients with adverse events in both groups	adverse events within first 3 months after the intervention	3 months

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Investigators: Principal Investigator: Cyriel Y Ponsioen, dr., Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Publications and helpful links

General Publications

• Ponsioen CY, Arnelo U, Bergquist A, Rauws EA, Paulsen V, Cantu P, Parzanese I, De Vries EM, van Munster KN, Said K, Chazouilleres O, Desaint B, Kemgang A, Farkkila M, Van der Merwe S, Van Steenbergen W, Marschall HU, Stotzer PO, Thorburn D, Pereira SP, Aabakken L. No Superiority of Stents vs Balloon Dilatation for Dominant Strictures in Patients With Primary Sclerosing Cholangitis. Gastroenterology. 2018 Sep;155(3):752-759.e5. doi: 10.1053/j.gastro.2018.05.034. Epub 2018 May 24.

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Anticipated): May 1, 2015
• Study Completion (Anticipated): May 1, 2015

Study Registration Dates

• First Submitted: April 25, 2011
• First Submitted That Met QC Criteria: July 20, 2011
• First Posted (Estimate): July 21, 2011

Study Record Updates

• Last Update Posted (Estimate): July 9, 2012
• Last Update Submitted That Met QC Criteria: July 5, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: psc; dominant stricture
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathological Conditions, Anatomical; Biliary Tract Diseases; Bile Duct Diseases; Constriction, Pathologic; Cholangitis; Cholangitis, Sclerosing
• Other Study ID Numbers: DILSTENT2; NL34454.018.10 (Registry Identifier: CCMO, Netherlands)