Clinical trial NCT04133792: Effect of Simvastatin on the Prognosis of Primary Primary Sclerosing Cholangitis (PSC)
Official title: Effect of Simvastatin on the Prognosis of Primary Sclerosing Cholangitis (PSC); A Randomized, Double-blind, Placebo Controlled Multicenter Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Primary Sclerosing Cholangitis
Lead sponsor: Karolinska University Hospital
Sponsor class: OTHER
First posted: 2019-10-21
Enrollment: 700
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Overall survival
timeFrame: Time from the date of randomization to the date of death, assessed up to 5 years.
measure: Listing for liver transplantation
timeFrame: Time from the date of randomization to the date of listing for liver transplantation, assessed up to 5 years.
measure: Time to first varices bleeding
timeFrame: Time from the date of randomization to the date of the first varices bleeding, assessed up to 5 years.
measure: Time to diagnosis of cholangiocarcinoma, gall bladder cancer, or hepatocellular cancer.
timeFrame: Time from the date of randomization to cancer diagnosis, assessed up to 5 years.
Secondary outcomes:
measure: Effect on serum concentration of alkaline phosphatase (ALP).
timeFrame: Assessed yearly up to 5 years.
measure: Effect on serum concentration of bilirubin
timeFrame: Assessed yearly up to 5 years.
measure: Effect on the progress of PSC by liver failure measurement
timeFrame: Assessed at every visit except the 3 months visit, up to 5 years.
measure: Effect on the progress of PSC by liver failure measurement.
timeFrame: Assessed at every visit except the 3 months visit, up to 5 years.
measure: Effect on the progress of PSC assessed by cholangiography at MRI.
timeFrame: Assessed at inclusion and the 60 months visit.
measure: Effect on the progress of PSC assessed by elastography
timeFrame: Assessed yearly up to 5 years.
measure: Effect on the progress of PSC assessed by clinical symptoms
timeFrame: Assessed yearly up to 5 years.
measure: Effect on the progress of PSC assessed by measurement of biliary dysplasia
timeFrame: Assessed upon clinical indication, up to 5 years.
measure: Effect on the development of colon cancer or colon dysplasia.
timeFrame: Assessed at 60 months.
measure: Effect on the progress of PSC assessed by serum fibrosis markers
timeFrame: Assessed yearly up to 5 years
Other outcomes:
Locations:
city: Malmö
country: Sweden
facility: Skåne Universitetssjukhus
state: Skåne
city: Umeå
country: Sweden
facility: Norrlands Universitetssjukhus
state: Västerbotten
city: Göteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset
state: Västra Götaland
city: Borås
country: Sweden
facility: Södra Älvsborgs sjukhus
city: Göteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset Östra
city: Karlstad
country: Sweden
facility: Karlstads centralsjukhus
city: Stockholm
country: Sweden
facility: Capio S:t Görans sjukhus
city: Stockholm
country: Sweden
facility: Ersta sjukhus
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Stockholm
country: Sweden
facility: Karolinska University Hospital Solna
city: Stockholm
country: Sweden
facility: Danderyds sjukhus
city: Trollhättan
country: Sweden
facility: Norra Älvsborgs länssjukhus
city: Uppsala
country: Sweden
facility: Akademiska sjukhuset
city: Örebro
country: Sweden
facility: Örebro Universitetssjukhus
city: Linköping
country: Sweden
facility: Universitetssjukhuset i Linköping
state: Östergötland
Study officials:
affiliation: Karolinska University Hospital
name: Annika Bergquist, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: