Primary Sclerosing Cholangitis
Conditions
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.
Detailed description
Please see published protocol Long Term Effect of Simvastatin in Primary Sclerosing Cholangitits: A Placebo-Controlled, Double-Blind, Multicenter Phase III Study (Piscatin) A. Bergquist, H. U. Marschall, E. Nilsson, N. Nyhlin, M. Werner, A. Klein, et al. British Journal of Gastroenterolgy 2022 Vol. 1 Pages 235-241.
Interventions
DRUGSimvastatin 40mg
40 mg orally daily for 5 years.
DRUGPlacebo oral tablet
40 mg orally daily for 5 years.
Sponsors
Annika Bergquist
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 elastography | Assessed yearly up to 5 years. | Assessment of fibrosis stage using elastography. |
| 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 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 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 serum fibrosis markers | Assessed yearly up to 5 years | Fib-4, ELF (if funded) |
| 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 serum concentration of bilirubin | Assessed yearly up to 5 years. | Assessment of changes in the serum concentration of bilirubin. |
| 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 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 |
Countries
Sweden
Outcome results
None listed