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

Primary Sclerosing Cholangitis Clinical Trial

— PiSCATIN  

Official title:

Effect of Simvastatin on the Prognosis of Primary Sclerosing Cholangitis (PSC); A Randomized, Double-blind, Placebo Controlled Multicenter Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04133792
• Other study ID #: 2018-000814-39
• Status: Recruiting
• Phase: Phase 3
• Start date: October 1, 2020
• Est. completion date: May 15, 2027

Study information

• Verified date: October 2022
• Source: Karolinska University Hospital
• Contact: Annika Bergquist, MD PhD
• Phone: 0707214907
• Email: annika.bergquist[@]ki.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 700
• Est. completion date: May 15, 2027
• Est. primary completion date: May 15, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cholangitis
• Cholangitis, Sclerosing
• Primary Sclerosing Cholangitis

Intervention

Drug:
• Simvastatin 40mg
40 mg orally daily for 5 years.
• Placebo oral tablet
40 mg orally daily for 5 years.

Locations

Country	Name	City	State
Sweden	Södra Älvsborgs sjukhus	Borås
Sweden	Sahlgrenska Universitetssjukhuset	Göteborg	Västra Götaland
Sweden	Sahlgrenska Universitetssjukhuset Östra	Göteborg
Sweden	Karlstads centralsjukhus	Karlstad
Sweden	Universitetssjukhuset i Linköping	Linköping	Östergötland
Sweden	Skåne Universitetssjukhus	Malmö	Skåne
Sweden	Örebro Universitetssjukhus	Örebro
Sweden	Capio S:t Görans sjukhus	Stockholm
Sweden	Danderyds sjukhus	Stockholm
Sweden	Ersta sjukhus	Stockholm
Sweden	Karolinska University Hospital	Stockholm
Sweden	Karolinska University Hospital Solna	Stockholm
Sweden	Norra Älvsborgs länssjukhus	Trollhättan
Sweden	Norrlands Universitetssjukhus	Umeå	Västerbotten
Sweden	Akademiska sjukhuset	Uppsala

Sponsors (1)

Lead Sponsor	Collaborator
Annika Bergquist

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival	Overall survival from time to randomization to death from any cause.	Time from the date of randomization to the date of death, assessed up to 5 years.
Primary	Listing for liver transplantation	Date the subject is getting registered on the waiting list for liver transplantation.	Time from the date of randomization to the date of listing for liver transplantation, assessed up to 5 years.
Primary	Time to first varices bleeding	Date of the subject's first varices bleeding according to hospital patient records.	Time from the date of randomization to the date of the first varices bleeding, assessed up to 5 years.
Primary	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 from the date of randomization to cancer diagnosis, assessed up to 5 years.
Secondary	Effect on serum concentration of alkaline phosphatase (ALP).	Assessment of changes in the serum concentration of alkaline phosphatase.	Assessed yearly up to 5 years.
Secondary	Effect on serum concentration of bilirubin	Assessment of changes in the serum concentration of bilirubin.	Assessed yearly up to 5 years.
Secondary	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).	Assessed at every visit except the 3 months visit, up to 5 years.
Secondary	Effect on the progress of PSC by liver failure measurement.	Assessment of liver failure using Child Pugh Score	Assessed at every visit except the 3 months visit, up to 5 years.
Secondary	Effect on the progress of PSC assessed by cholangiography at MRI.	Progress assessed by cholangiography MRI	Assessed at inclusion and the 60 months visit.
Secondary	Effect on the progress of PSC assessed by elastography	Assessment of fibrosis stage using elastography.	Assessed yearly up to 5 years.
Secondary	Effect on the progress of PSC assessed by clinical symptoms	Assessment of symptoms including itching and bacterial cholangitis that requires treatment, ascites and encephalopathy.	Assessed yearly up to 5 years.
Secondary	Effect on the progress of PSC assessed by measurement of biliary dysplasia	Biliary dysplasia from brush samples taken at endoscopic retrograde cholangiopancreatography (ERCP).	Assessed upon clinical indication, up to 5 years.
Secondary	Effect on the development of colon cancer or colon dysplasia.	Development of colon cancer and/or colon dysplasia according to hospital patient records.	Assessed at 60 months.
Secondary	Effect on the progress of PSC assessed by serum fibrosis markers	Fib-4, ELF (if funded)	Assessed yearly up to 5 years