Effect of Simvastatin on the Prognosis of Primary Primary Sclerosing Cholangitis (PSC)

Phase 3Active Not RecruitingNCT04133792

Annika Bergquist571 enrolled

Overview

This is a randomized, double-blind, placebo controlled multicenter study. A total of 700 patients will be included. After an updated powercalculation 560 was condidered enough The study will include patients with primary sclerosing cholangitis (PSC) for daily intake of 40 mg simvastatin/placebo for 5 years. The aim is to study effect of prognosis of PSC by long term intake of simvastatin. Outcome measures are death, liver transplantation, cholangiocarcinoma or bleeding from esophageal varices. Subjects will be randomized (1:1) between Simvastatin and placebo.

Please see published protocol Long Term Effect of Simvastatin in Primary Sclerosing Cholangitits: A Placebo-Controlled, Double-Blind, Multicenter Phase III Study (Piscatin) A. Bergquist, H. U. Marschall, E. Nilsson, N. Nyhlin, M. Werner, A. Klein, et al. British Journal of Gastroenterolgy 2022 Vol. 1 Pages 235-241.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

571

Conditions

Primary Sclerosing Cholangitis

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * PSC verified by cholangiography or liver biopsy, with or without irritable bowel disease (IBD). * Men and women between ≥18 years and ≤75 years. * Written informed consent. * A magnetic resonance imaging (MRI) or Magnetic resonance cholangiopancreatography (MRCP) performed within 4 months prior to randomization. * Colonoscopy performed within 24 months prior to randomization, if known IBD. * For women of childbearing potential efficient contraceptive. Exclusion Criteria: * Subjects on waiting list for transplantation * Transplanted subjects * Previous variceal bleeding * Previous hepatobiliary malignancy * Subjects with secondary sclerosing cholangitis * Intake of any type of statins within 3 months prior to randmization * Known intolerance to simvastatin. * Pregnancy or breastfeeding.

Locations (12)

Skåne Universitetssjukhus

Malmö, Skåne County, Sweden

Norrlands Universitetssjukhus

Umeå, Västerbotten County, Sweden

Sahlgrenska Universitetssjukhuset

Gothenburg, Västra Götaland County, Sweden

Sahlgrenska Universitetssjukhuset Östra

Gothenburg, Sweden

Karlstads centralsjukhus

Karlstad, Sweden

Skaraborgs sjukhus

Lidköping, Sweden

Örebro Universitetssjukhus

Örebro, Sweden

Karolinska University Hospital

Stockholm, Sweden

Karolinska University Hospital Solna

Stockholm, Sweden

Danderyds sjukhus

Stockholm, Sweden

...and 2 more locations

Outcomes

Primary Outcomes

Overall survival

Overall survival from time to randomization to death from any cause.

Time frame: Time from the date of randomization to the date of death, assessed up to 5 years.

Listing for liver transplantation

Date the subject is getting registered on the waiting list for liver transplantation.

Time frame: Time from the date of randomization to the date of listing for liver transplantation, assessed up to 5 years.

Time to first varices bleeding

Date of the subject's first varices bleeding according to hospital patient records.

Time frame: Time from the date of randomization to the date of the first varices bleeding, assessed up to 5 years.

Time to diagnosis of cholangiocarcinoma, gall bladder cancer, or hepatocellular cancer.

Diagnosis of cancer of bile duct cancer or gall bladder, or hepatocellular cancer according to hospital patient records.

Time frame: Time from the date of randomization to cancer diagnosis, assessed up to 5 years.

Secondary Outcomes

Effect on serum concentration of alkaline phosphatase (ALP).

Assessment of changes in the serum concentration of alkaline phosphatase.

Time frame: Assessed yearly up to 5 years.

Effect on serum concentration of bilirubin

Assessment of changes in the serum concentration of bilirubin.

Time frame: Assessed yearly up to 5 years.

Effect on the progress of PSC by liver failure measurement

Assessment of liver failure using Model for End Stage Liver Disease (MELD) Score (biochemical and clinical variables).

Time frame: Assessed at every visit except the 3 months visit, up to 5 years.

Effect on the progress of PSC by liver failure measurement.

Assessment of liver failure using Child Pugh Score

Time frame: Assessed at every visit except the 3 months visit, up to 5 years.

Effect on the progress of PSC assessed by cholangiography at MRI.

Progress assessed by cholangiography MRI

Time frame: Assessed at inclusion and the 60 months visit.

Effect on the progress of PSC assessed by elastography

Assessment of fibrosis stage using elastography.

Time frame: Assessed yearly up to 5 years.

Effect on the progress of PSC assessed by clinical symptoms

Assessment of symptoms including itching and bacterial cholangitis that requires treatment, ascites and encephalopathy.

Time frame: Assessed yearly up to 5 years.

Effect on the progress of PSC assessed by measurement of biliary dysplasia

Biliary dysplasia from brush samples taken at endoscopic retrograde cholangiopancreatography (ERCP).

Time frame: Assessed upon clinical indication, up to 5 years.

Effect on the development of colon cancer or colon dysplasia.

Development of colon cancer and/or colon dysplasia according to hospital patient records.

Time frame: Assessed at 60 months.

Effect on the progress of PSC assessed by serum fibrosis markers

Fib-4, ELF (if funded)

Time frame: Assessed yearly up to 5 years