NCT04133792

Brief Summary

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.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
571

participants targeted

Target at P75+ for phase_3

Timeline
48mo left

Started Oct 2020

Longer than P75 for phase_3

Geographic Reach
1 country

12 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress59%
Oct 2020Mar 2030

First Submitted

Initial submission to the registry

October 17, 2019

Completed
4 days until next milestone

First Posted

Study publicly available on registry

October 21, 2019

Completed
12 months until next milestone

Study Start

First participant enrolled

October 1, 2020

Completed
7.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 31, 2028

Expected
2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 31, 2030

Last Updated

September 5, 2025

Status Verified

August 1, 2025

Enrollment Period

7.5 years

First QC Date

October 17, 2019

Last Update Submit

August 29, 2025

Conditions

Primary Sclerosing Cholangitis

Outcome Measures

Primary Outcomes (4)

  • 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.

  • 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.

  • 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.

  • 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 Outcomes (10)

  • Effect on serum concentration of alkaline phosphatase (ALP).

    Assessed yearly up to 5 years.

  • Effect on serum concentration of bilirubin

    Assessed yearly up to 5 years.

  • Effect on the progress of PSC by liver failure measurement

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

  • Effect on the progress of PSC by liver failure measurement.

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

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

    Assessed at inclusion and the 60 months visit.

  • +5 more secondary outcomes

Study Arms (2)

Simvastatin

EXPERIMENTAL

Simvastatin 40 mg administered orally daily for 5 years.

Drug: Simvastatin 40mg

Placebo

PLACEBO COMPARATOR

Placebo for Simvastatin 40 mg administered orally daily for 5 years.

Drug: Placebo oral tablet

Interventions

Simvastatin 40mgDRUG

40 mg orally daily for 5 years.

Simvastatin
Placebo oral tabletDRUG

40 mg orally daily for 5 years.

Placebo

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (12)

Skåne Universitetssjukhus

Malmo, Skåne County, 222 42, Sweden

Location

Norrlands Universitetssjukhus

Umeå, Västerbotten County, 907 37, Sweden

Location

Sahlgrenska Universitetssjukhuset

Gothenburg, Västra Götaland County, 413 45, Sweden

Location

Sahlgrenska Universitetssjukhuset Östra

Gothenburg, 41685, Sweden

Location

Karlstads centralsjukhus

Karlstad, 652 30, Sweden

Location

Skaraborgs sjukhus

Lidköping, Sweden

Location

Örebro Universitetssjukhus

Örebro, 701 85, Sweden

Location

Karolinska University Hospital

Stockholm, 141 57, Sweden

Location

Karolinska University Hospital Solna

Stockholm, 171 64, Sweden

Location

Danderyds sjukhus

Stockholm, 182 57, Sweden

Location

Akademiska sjukhuset

Uppsala, 751 85, Sweden

Location

Universitetssjukhuset i Linköping

Linköping, Östergötland County, 581 85, Sweden

Location

Related Publications (1)

  • Lindqvist C, Ingre M, Kechagias S, Nilsson E, Molinaro A, Rorsman F, Bergquist A. Dietary Habits of Individuals With Primary Sclerosing Cholangitis-Poor Fat-Soluble Vitamin Intake and Dietary Quality. Liver Int. 2025 Apr;45(4):e16182. doi: 10.1111/liv.16182. Epub 2024 Nov 27.

    PMID: 39601354DERIVED

MeSH Terms

Conditions

Cholangitis, Sclerosing

Interventions

Simvastatin

Condition Hierarchy (Ancestors)

CholangitisBile Duct DiseasesBiliary Tract DiseasesDigestive System Diseases

Intervention Hierarchy (Ancestors)

LovastatinNaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic Compounds

Study Officials

  • Annika Bergquist, MD PhD

    Karolinska University Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

October 17, 2019

First Posted

October 21, 2019

Study Start

October 1, 2020

Primary Completion (Estimated)

March 31, 2028

Study Completion (Estimated)

March 31, 2030

Last Updated

September 5, 2025

Record last verified: 2025-08

Data Sharing

IPD Sharing
Will not share

Locations

SE(12)