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

Primary Sclerosing Cholangitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01398917
• Other study ID #: DILSTENT2
• Secondary ID: NL34454.018.10
• Status: Recruiting
• Phase: Phase 3
• First received: April 25, 2011
• Last updated: July 5, 2012
• Start date: May 2011
• Est. completion date: May 2015

Study information

• Verified date: July 2012
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: Cyriel Y Ponsioen, Dr.
• Phone: +31 20 5666012
• Email: c.y.ponsioen[@]amc.nl
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cholangitis
• Cholangitis, Sclerosing
• Primary Sclerosing Cholangitis

Intervention

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
• balloon dilatation
4 cm 6 mm biliary dilatation balloon to be inflated for 2 minutes in dominant stricture(s)

Locations

Country	Name	City	State
Belgium	UZLeuven	Leuven
Netherlands	Academic Medical Center	Amsterdam
Norway	Rikshospitalet	Oslo
Sweden	Karolinska Institute	Stockholm

Sponsors (1)

Lead Sponsor	Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Countries where clinical trial is conducted

Belgium,  Netherlands,  Norway,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	recurrence-free interval of the primary dominant stricture		24 months	No
Secondary	number of patients with adverse events in both groups	adverse events within first 3 months after the intervention	3 months	Yes