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

Phase 3

Recruiting

• Conditions: Primary Sclerosing Cholangitis
• Interventions: Drug: Simvastatin 40mg; Drug: Placebo oral tablet

• Registration Number: NCT04133792
• Lead Sponsor: Annika Bergquist

Brief Summary

This is a randomized, double-blind, placebo controlled multicenter study.

A total of 700 patients will be included.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-10-17
• Study First Submitted QC: 2019-10-17
• Study First Posted: 2019-10-21
• Study Start: 2020-10-01
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-31
• Last Update Posted: 2022-11-01
• Primary Completion: 2027-05-15
• Study Completion: 2027-05-15

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 700

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Simvastatin	Simvastatin 40mg	Simvastatin 40 mg administered orally daily for 5 years.
Placebo	Placebo oral tablet	Placebo for Simvastatin 40 mg administered orally daily for 5 years.

Primary Outcome Measures

Name	Time	Method
Overall survival	Time from the date of randomization to the date of death, assessed up to 5 years.	Overall survival from time to randomization to death from any cause.
Time to diagnosis of cholangiocarcinoma, gall bladder cancer, or hepatocellular cancer.	Time from the date of randomization to cancer diagnosis, assessed up to 5 years.	Diagnosis of cancer of bile duct cancer or gall bladder, or hepatocellular cancer according to hospital patient records.
Time to first varices bleeding	Time from the date of randomization to the date of the first varices bleeding, assessed up to 5 years.	Date of the subject's first varices bleeding according to hospital patient records.
Listing for liver transplantation	Time from the date of randomization to the date of listing for liver transplantation, assessed up to 5 years.	Date the subject is getting registered on the waiting list for liver transplantation.

Secondary Outcome Measures

Name	Time	Method
Effect on the progress of PSC by liver failure measurement	Assessed at every visit except the 3 months visit, up to 5 years.	Assessment of liver failure using Model for End Stage Liver Disease (MELD) Score (biochemical and clinical variables).
Effect on serum concentration of bilirubin	Assessed yearly up to 5 years.	Assessment of changes in the serum concentration of bilirubin.
Effect on serum concentration of alkaline phosphatase (ALP).	Assessed yearly up to 5 years.	Assessment of changes in the serum concentration of alkaline phosphatase.
Effect on the progress of PSC by liver failure measurement.	Assessed at every visit except the 3 months visit, up to 5 years.	Assessment of liver failure using Child Pugh Score
Effect on the progress of PSC assessed by elastography	Assessed yearly up to 5 years.	Assessment of fibrosis stage using elastography.
Effect on the progress of PSC assessed by measurement of biliary dysplasia	Assessed upon clinical indication, up to 5 years.	Biliary dysplasia from brush samples taken at endoscopic retrograde cholangiopancreatography (ERCP).
Effect on the development of colon cancer or colon dysplasia.	Assessed at 60 months.	Development of colon cancer and/or colon dysplasia according to hospital patient records.
Effect on the progress of PSC assessed by clinical symptoms	Assessed yearly up to 5 years.	Assessment of symptoms including itching and bacterial cholangitis that requires treatment, ascites and encephalopathy.
Effect on the progress of PSC assessed by cholangiography at MRI.	Assessed at inclusion and the 60 months visit.	Progress assessed by cholangiography MRI
Effect on the progress of PSC assessed by serum fibrosis markers	Assessed yearly up to 5 years	Fib-4, ELF (if funded)

Trial Locations

Locations (15)

Skåne Universitetssjukhus; 🇸🇪 Malmö, Skåne, Sweden

Karlstads centralsjukhus; 🇸🇪 Karlstad, Sweden

Örebro Universitetssjukhus; 🇸🇪 Örebro, Sweden

Universitetssjukhuset i Linköping; 🇸🇪 Linköping, Östergötland, Sweden

Norrlands Universitetssjukhus; 🇸🇪 Umeå, Västerbotten, Sweden

Sahlgrenska Universitetssjukhuset; 🇸🇪 Göteborg, Västra Götaland, Sweden

Södra Älvsborgs sjukhus; 🇸🇪 Borås, Sweden

Sahlgrenska Universitetssjukhuset Östra; 🇸🇪 Göteborg, Sweden

Ersta sjukhus; 🇸🇪 Stockholm, Sweden

Karolinska University Hospital; 🇸🇪 Stockholm, Sweden

Capio S:t Görans sjukhus; 🇸🇪 Stockholm, Sweden

Danderyds sjukhus; 🇸🇪 Stockholm, Sweden

Akademiska sjukhuset; 🇸🇪 Uppsala, Sweden

Karolinska University Hospital Solna; 🇸🇪 Stockholm, Sweden

Norra Älvsborgs länssjukhus; 🇸🇪 Trollhättan, Sweden