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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04133792
Recruitment Status : Not yet recruiting
First Posted : October 21, 2019
Last Update Posted : October 28, 2019
Sponsor:
Information provided by (Responsible Party):
Annika Bergquist, Karolinska University Hospital

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.


Condition or disease Intervention/treatment Phase
Primary Sclerosing Cholangitis Drug: Simvastatin 40mg Drug: Placebo oral tablet Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 700 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Simvastatin on the Prognosis of Primary Sclerosing Cholangitis (PSC); A Randomized, Double-blind, Placebo Controlled Multicenter Study
Estimated Study Start Date : May 15, 2020
Estimated Primary Completion Date : May 15, 2027
Estimated Study Completion Date : May 15, 2027


Arm Intervention/treatment
Experimental: Simvastatin
Simvastatin 40 mg administered orally daily for 5 years.
Drug: Simvastatin 40mg
40 mg orally daily for 5 years.

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




Primary Outcome Measures :
  1. Overall survival [ Time Frame: 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.

  2. Listing for liver transplantation [ Time Frame: 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.

  3. Time to first varices bleeding [ Time Frame: 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.

  4. Time to diagnosis of cholangiocarcinoma, gall bladder cancer, or hepatocellular cancer. [ Time Frame: 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.


Secondary Outcome Measures :
  1. Effect on serum concentration of alkaline phosphatase (ALP). [ Time Frame: Assessed yearly up to 5 years. ]
    Assessment of changes in the serum concentration of alkaline phosphatase.

  2. Effect on serum concentration of bilirubin [ Time Frame: Assessed yearly up to 5 years. ]
    Assessment of changes in the serum concentration of bilirubin.

  3. Effect on the progress of PSC by liver failure measurement [ Time Frame: 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).

  4. Effect on the progress of PSC by liver failure measurement. [ Time Frame: Assessed at every visit except the 3 months visit, up to 5 years. ]
    Assessment of liver failure using Child Pugh Score

  5. Effect on the progress of PSC assessed by cholangiography at MRI. [ Time Frame: Assessed at inclusion and the 60 months visit. ]
    Progress assessed by cholangiography MRI

  6. Effect on the progress of PSC assessed by elastography [ Time Frame: Assessed yearly up to 5 years. ]
    Assessment of fibrosis stage using elastography.

  7. Effect on the progress of PSC assessed by clinical symptoms [ Time Frame: Assessed yearly up to 5 years. ]
    Assessment of symptoms including itching and bacterial cholangitis that requires treatment, ascites and encephalopathy.

  8. Effect on the progress of PSC assessed by measurement of biliary dysplasia [ Time Frame: Assessed upon clinical indication, up to 5 years. ]
    Biliary dysplasia from brush samples taken at endoscopic retrograde cholangiopancreatography (ERCP).

  9. Effect on the development of colon cancer or colon dysplasia. [ Time Frame: Assessed at 60 months. ]
    Development of colon cancer and/or colon dysplasia according to hospital patient records.

  10. Effect on the progress of PSC assessed by serum fibrosis markers [ Time Frame: Assessed yearly up to 5 years ]
    Fib-4, ELF (if funded)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04133792


Contacts
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Contact: Annika Bergquist, MD PhD 0707214907 ext +46 annika.bergquist@ki.se
Contact: Amanda Klein, PhD 08-524 837 32 ext +46 amanda.klein@ki.se

Sponsors and Collaborators
Annika Bergquist

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Responsible Party: Annika Bergquist, Professor, Karolinska University Hospital
ClinicalTrials.gov Identifier: NCT04133792    
Other Study ID Numbers: 2018-000814-39
First Posted: October 21, 2019    Key Record Dates
Last Update Posted: October 28, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Cholangitis
Cholangitis, Sclerosing
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Simvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors